Peter G D'Eustachio, Ph.D.

The representation of protein complexes in the Protein Ontology (PRO)
Bult, Carol J; Drabkin, Harold J; Evsikov, Alexei; Natale, Darren; Arighi, Cecilia; Roberts, Natalia; Ruttenberg, Alan; D'Eustachio, Peter; Smith, Barry; Blake, Judith A; Wu, Cathy
2011 ;12:371-371, BMC bioinformatics
ABSTRACT: BACKGROUND: Representing species-specific proteins and protein complexes in ontologies that are both human- and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. DESCRIPTION: We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. CONCLUSION: PRO is a unique database resource for species-specific protein complexes. PRO facilitates robust annotation of variations in composition and function contexts for protein complexes within and between species
— id: 139625, year: 2011, vol: 12, page: 371, stat: Journal Article,

Reactome: a database of reactions, pathways and biological processes
Croft, David; O'Kelly, Gavin; Wu, Guanming; Haw, Robin; Gillespie, Marc; Matthews, Lisa; Caudy, Michael; Garapati, Phani; Gopinath, Gopal; Jassal, Bijay; Jupe, Steven; Kalatskaya, Irina; Mahajan, Shahana; May, Bruce; Ndegwa, Nelson; Schmidt, Esther; Shamovsky, Veronica; Yung, Christina; Birney, Ewan; Hermjakob, Henning; D'Eustachio, Peter; Stein, Lincoln
2011 Jan;39(Database issue):D691-D697, Nucleic acids research
Reactome (http://www.reactome.org) is a collaboration among groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University School of Medicine and The European Bioinformatics Institute, to develop an open source curated bioinformatics database of human pathways and reactions. Recently, we developed a new web site with improved tools for pathway browsing and data analysis. The Pathway Browser is an Systems Biology Graphical Notation (SBGN)-based visualization system that supports zooming, scrolling and event highlighting. It exploits PSIQUIC web services to overlay our curated pathways with molecular interaction data from the Reactome Functional Interaction Network and external interaction databases such as IntAct, BioGRID, ChEMBL, iRefIndex, MINT and STRING. Our Pathway and Expression Analysis tools enable ID mapping, pathway assignment and overrepresentation analysis of user-supplied data sets. To support pathway annotation and analysis in other species, we continue to make orthology-based inferences of pathways in non-human species, applying Ensembl Compara to identify orthologs of curated human proteins in each of 20 other species. The resulting inferred pathway sets can be browsed and analyzed with our Species Comparison tool. Collaborations are also underway to create manually curated data sets on the Reactome framework for chicken, Drosophila and rice
— id: 134144, year: 2011, vol: 39, page: D691, stat: Journal Article,

Reactome knowledgebase of human biological pathways and processes
D'Eustachio, Peter
2011 ;694:49-61, Methods in molecular biology
The Reactome Knowledgebase is an online, manually curated resource that provides an integrated view of the molecular details of human biological processes that range from metabolism to DNA replication and repair to signaling cascades. Its data model allows these diverse processes to be represented in a consistent way to facilitate usage as online text and as a resource for data mining, modeling, and analysis of large-scale expression data sets over the full range of human biological processes
— id: 114590, year: 2011, vol: 694, page: 49, stat: Journal Article,

Human and chicken TLR pathways: manual curation and computer-based orthology analysis
Gillespie, Marc; Shamovsky, Veronica; D'Eustachio, Peter
2011 Feb;22(1-2):130-138, Mammalian genome
The innate immune responses mediated by Toll-like receptors (TLR) provide an evolutionarily well-conserved first line of defense against microbial pathogens. In the Reactome Knowledgebase we previously integrated annotations of human TLR molecular functions with those of over 4000 other human proteins involved in processes such as adaptive immunity, DNA replication, signaling, and intermediary metabolism, and have linked these annotations to external resources, including PubMed, UniProt, EntrezGene, Ensembl, and the Gene Ontology to generate a resource suitable for data mining, pathway analysis, and other systems biology approaches. We have now used a combination of manual expert curation and computer-based orthology analysis to generate a set of annotations for TLR molecular function in the chicken (Gallus gallus). Mammalian and avian lineages diverged approximately 300 million years ago, and the avian TLR repertoire consists of both orthologs and distinct new genes. The work described here centers on the molecular biology of TLR3, the host receptor that mediates responses to viral and other doubled-stranded polynucleotides, as a paradigm for our approach to integrated manual and computationally based annotation and data analysis. It tests the quality of computationally generated annotations projected from human onto other species and supports a systems biology approach to analysis of virus-activated signaling pathways and identification of clinically useful antiviral measures
— id: 134159, year: 2011, vol: 22, page: 130, stat: Journal Article,

Reactome pathway analysis to enrich biological discovery in proteomics data sets
Haw, Robin; Hermjakob, Henning; D'Eustachio, Peter; Stein, Lincoln
2011 Sep;11(18):3598-3613, Proteomics
Reactome (http://www.reactome.org) is an open-source, expert-authored, peer-reviewed, manually curated database of reactions, pathways and biological processes. We provide an intuitive web-based user interface to pathway knowledge and a suite of data analysis tools. The Pathway Browser is a Systems Biology Graphical Notation-like visualization system that supports manual navigation of pathways by zooming, scrolling and event highlighting, and that exploits PSI Common Query Interface web services to overlay pathways with molecular interaction data from the Reactome Functional Interaction Network and interaction databases such as IntAct, ChEMBL and BioGRID. Pathway and expression analysis tools employ web services to provide ID mapping, pathway assignment and over-representation analysis of user-supplied data sets. By applying Ensembl Compara to curated human proteins and reactions, Reactome generates pathway inferences for 20 other species. The Species Comparison tool provides a summary of results for each of these species as a table showing numbers of orthologous proteins found by pathway from which users can navigate to inferred details for specific proteins and reactions. Reactome's diverse pathway knowledge and suite of data analysis tools provide a platform for data mining, modeling and analysis of large-scale proteomics data sets. This Tutorial is part of the International Proteomics Tutorial Programme (IPTP 8)
— id: 150116, year: 2011, vol: 11, page: 3598, stat: Journal Article,

The Protein Ontology: a structured representation of protein forms and complexes
Natale, Darren A; Arighi, Cecilia N; Barker, Winona C; Blake, Judith A; Bult, Carol J; Caudy, Michael; Drabkin, Harold J; D'Eustachio, Peter; Evsikov, Alexei V; Huang, Hongzhan; Nchoutmboube, Jules; Roberts, Natalia V; Smith, Barry; Zhang, Jian; Wu, Cathy H
2011 Jan;39(Database issue):D539-D545, Nucleic acids research
The Protein Ontology (PRO) provides a formal, logically-based classification of specific protein classes including structured representations of protein isoforms, variants and modified forms. Initially focused on proteins found in human, mouse and Escherichia coli, PRO now includes representations of protein complexes. The PRO Consortium works in concert with the developers of other biomedical ontologies and protein knowledge bases to provide the ability to formally organize and integrate representations of precise protein forms so as to enhance accessibility to results of protein research. PRO (http://pir.georgetown.edu/pro) is part of the Open Biomedical Ontology Foundry
— id: 134145, year: 2011, vol: 39, page: D539, stat: Journal Article,

The Gene Ontology in 2010: extensions and refinements The Gene Ontology Consortium
Berardini, TZ; Li, DH; Huala, E; Bridges, S; Burgess, S; McCarthy, F; Carbon, S; Lewis, SE; Mungall, CJ; Abdulla, A; Wood, V; Feltrin, E; Valle, G; Chisholm, RL; Fey, P; Gaudet, P; Kibbe, W; Basu, S; Bushmanova, Y; Eilbeck, K; Siegele, DA; McIntosh, B; Renfro, D; Zweifel, A; Hu, JC; Ashburner, M; Tweedie, S; Alam-Faruque, Y; Apweiler, R; Auchinchloss, A; Bairoch, A; Barrell, D; Binns, D; Blatter, MC; Bougueleret, L; Boutet, E; Breuza, L; Bridge, A; Browne, P; Chan, WM; Coudert, E; Daugherty, L; Dimmer, E; Eberhardt, R; Estreicher, A; Famiglietti, L; Ferro-Rojas, S; Feuermann, M; Foulger, R; Gruaz-Gumowski, N; Hinz, U; Huntley, R; Jimenez, S; Jungo, F; Keller, G; Laiho, K; Legge, D; Lemercier, P; Lieberherr, D; Magrane, M; O'Donovan, C; Pedruzzi, I; Poux, S; Rivoire, C; Roechert, B; Sawford, T; Schneider, M; Stanley, E; Stutz, A; Sundaram, S; Tognolli, M; Xenarios, I; Harris, MA; Deegan, JI; Ireland, A; Lomax, J; Jaiswal, P; Chibucos, M; Giglio, MG; Wortman, J; Hannick, L; Madupu, R; Botstein, D; Dolinski, K; Livstone, MS; Oughtred, R; Blake, JA; Bult, C; Diehl, AD; Dolan, M; Drabkin, H; Eppig, JT; Hill, DP; Ni, L; Ringwald, M; Sitnikov, D; Collmer, C; Torto-Alalibo, T; Laulederkind, S; Shimoyama, M; Twigger, S; D'Eustachio, P; Matthews, L; Balakrishnan, R; Binkley, G; Cherry, JM; Christie, KR; Costanzo, MC; Engel, SR; Fisk, DG; Hirschman, JE; Hitz, BC; Hong, EL; Krieger, CJ; Miyasato, SR; Nash, RS; Park, J; Skrzypek, MS; Weng, SA; Wong, ED; Aslett, M; Chan, J; Kishore, R; Sternberg, P; Van Auken, K; Khodiyar, VK; Lovering, RC; Talmud, PJ; Howe, D; Westerfield, M
2010 JAN ;38(4):D331-D335, Nucleic acids research
The Gene Ontology (GO) Consortium (http://www.geneontology.org) (GOC) continues to develop, maintain and use a set of structured, controlled vocabularies for the annotation of genes, gene products and sequences. The GO ontologies are expanding both in content and in structure. Several new relationship types have been introduced and used, along with existing relationships, to create links between and within the GO domains. These improve the representation of biology, facilitate querying, and allow GO developers to systematically check for and correct inconsistencies within the GO. Gene product annotation using GO continues to increase both in the number of total annotations and in species coverage. GO tools, such as OBO-Edit, an ontology-editing tool, and AmiGO, the GOC ontology browser, have seen major improvements in functionality, speed and ease of use
— id: 109067, year: 2010, vol: 38, page: D331, stat: Journal Article,

The BioPAX community standard for pathway data sharing
Demir, Emek; Cary, Michael P; Paley, Suzanne; Fukuda, Ken; Lemer, Christian; Vastrik, Imre; Wu, Guanming; D'Eustachio, Peter; Schaefer, Carl; Luciano, Joanne; Schacherer, Frank; Martinez-Flores, Irma; Hu, Zhenjun; Jimenez-Jacinto, Veronica; Joshi-Tope, Geeta; Kandasamy, Kumaran; Lopez-Fuentes, Alejandra C; Mi, Huaiyu; Pichler, Elgar; Rodchenkov, Igor; Splendiani, Andrea; Tkachev, Sasha; Zucker, Jeremy; Gopinath, Gopal; Rajasimha, Harsha; Ramakrishnan, Ranjani; Shah, Imran; Syed, Mustafa; Anwar, Nadia; Babur, Ozgun; Blinov, Michael; Brauner, Erik; Corwin, Dan; Donaldson, Sylva; Gibbons, Frank; Goldberg, Robert; Hornbeck, Peter; Luna, Augustin; Murray-Rust, Peter; Neumann, Eric; Reubenacker, Oliver; Samwald, Matthias; van Iersel, Martijn; Wimalaratne, Sarala; Allen, Keith; Braun, Burk; Whirl-Carrillo, Michelle; Cheung, Kei-Hoi; Dahlquist, Kam; Finney, Andrew; Gillespie, Marc; Glass, Elizabeth; Gong, Li; Haw, Robin; Honig, Michael; Hubaut, Olivier; Kane, David; Krupa, Shiva; Kutmon, Martina; Leonard, Julie; Marks, Debbie; Merberg, David; Petri, Victoria; Pico, Alex; Ravenscroft, Dean; Ren, Liya; Shah, Nigam; Sunshine, Margot; Tang, Rebecca; Whaley, Ryan; Letovksy, Stan; Buetow, Kenneth H; Rzhetsky, Andrey; Schachter, Vincent; Sobral, Bruno S; Dogrusoz, Ugur; McWeeney, Shannon; Aladjem, Mirit; Birney, Ewan; Collado-Vides, Julio; Goto, Susumu; Hucka, Michael; Le Novere, Nicolas; Maltsev, Natalia; Pandey, Akhilesh; Thomas, Paul; Wingender, Edgar; Karp, Peter D; Sander, Chris; Bader, Gary D
2010 Sep;28(9):935-942, Nature biotechnology
Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery
— id: 134350, year: 2010, vol: 28, page: 935, stat: Journal Article,

Time for DNA disclosure
Krane, D E; Bahn, V; Balding, D; Barlow, B; Cash, H; Desportes, B L; D'Eustachio, P; Devlin, K; Doom, T E; Dror, I; Ford, S; Funk, C; Gilder, J; Hampikian, G; Inman, K; Jamieson, A; Kent, P E; Koppl, R; Kornfield, I; Krimsky, S; Mnookin, J; Mueller, L; Murphy, E; Paoletti, D R; Petrov, D A; Raymer, M; Risinger, D M; Roth, A; Rudin, N; Shields, W; Siegel, J A; Slatkin, M; Song, Y S; Speed, T; Spiegelman, C; Sullivan, P; Swienton, A R; Tarpey, T; Thompson, W C; Ungvarsky, E; Zabell, S
2009 Dec 18;326(5960):1631-1632, Science
— id: 133741, year: 2009, vol: 326, page: 1631, stat: Journal Article,

Reactome knowledgebase of human biological pathways and processes
Matthews, Lisa; Gopinath, Gopal; Gillespie, Marc; Caudy, Michael; Croft, David; de Bono, Bernard; Garapati, Phani; Hemish, Jill; Hermjakob, Henning; Jassal, Bijay; Kanapin, Alex; Lewis, Suzanna; Mahajan, Shahana; May, Bruce; Schmidt, Esther; Vastrik, Imre; Wu, Guanming; Birney, Ewan; Stein, Lincoln; D'Eustachio, Peter
2009 Jan;37(Database issue):D619-D622, Nucleic acids research
Reactome (http://www.reactome.org) is an expert-authored, peer-reviewed knowledgebase of human reactions and pathways that functions as a data mining resource and electronic textbook. Its current release includes 2975 human proteins, 2907 reactions and 4455 literature citations. A new entity-level pathway viewer and improved search and data mining tools facilitate searching and visualizing pathway data and the analysis of user-supplied high-throughput data sets. Reactome has increased its utility to the model organism communities with improved orthology prediction methods allowing pathway inference for 22 species and through collaborations to create manually curated Reactome pathway datasets for species including Arabidopsis, Oryza sativa (rice), Drosophila and Gallus gallus (chicken). Reactome's data content and software can all be freely used and redistributed under open source terms
— id: 135220, year: 2009, vol: 37, page: D619, stat: Journal Article,

Reactome: a knowledge base of biologic pathways and processes (vol 8, pg 39, 2007)
Vastrik, I; D'Eustachio, P; Schmidt, E; Gopinath, G; Croft, D; de Bono, B; Gillespie, M; Jassal, B; Lewis, S; Matthews, L; Wu, G; Birney, E; Stein, L
2009 MAY 22 ;10(2):646-646, Genome biology
— id: 99303, year: 2009, vol: 10, page: 646, stat: Journal Article,

Arabidopsis reactome: A foundation knowledgebase for plant systems biology
Tsesmetzis, N; Couchman, M; Higgins, J; Smith, A; Doonan, JH; Seifert, GJ; Schmidt, EE; Vastrik, I; Birney, E; Wu, GM; D'Eustachio, P; Stein, LD; Morris, RJ; Bevan, MW; Walsh, SV
2008 JUN ;20(6):1426-1436, Plant Cell
New ways of capturing and representing biological knowledge are needed to enable individual researchers to remain abreast of relevant discoveries and to permit computational approaches for interpreting the large volumes of diverse data generated by modern biological research. Here, we describe a promising approach that expands the term 'reaction'' to represent biological processes. We show how users can represent a wide variety of biological processes in plants in terms of the concept of a reaction and assemble the information obtained from the model plant Arabidopsis thaliana into an online knowledgebase called Arabidopsis Reactome. Its curated and imported pathways currently cover similar to 8% of the Arabidopsis proteome. Arabidopsis Reactome events have also been electronically projected onto five other predicted plant proteomes. Such a system allows the visualization and interpretation of high-throughput data, hypothesis formulation in systems biology, and is a useful learning resource. The Arabidopsis Reactome project (www.arabidopsisreactome.org) is open access, open source, and open to contributions
— id: 86828, year: 2008, vol: 20, page: 1426, stat: Journal Article,

Reactome: a knowledge base of biologic pathways and processes
Vastrik, Imre; D'Eustachio, Peter; Schmidt, Esther; Gopinath, Gopal; Croft, David; de Bono, Bernard; Gillespie, Marc; Jassal, Bijay; Lewis, Suzanna; Matthews, Lisa; Wu, Guanming; Birney, Ewan; Stein, Lincoln
2007 ;8(3):R39-R39, Genome biology
Reactome http://www.reactome.org, an online curated resource for human pathway data, provides infrastructure for computation across the biologic reaction network. We use Reactome to infer equivalent reactions in multiple nonhuman species, and present data on the reliability of these inferred reactions for the distantly related eukaryote Saccharomyces cerevisiae. Finally, we describe the use of Reactome both as a learning resource and as a computational tool to aid in the interpretation of microarrays and similar large-scale datasets
— id: 79458, year: 2007, vol: 8, page: R39, stat: Journal Article,

An interaction between genetic factors and gender determines the magnitude of the inflammatory response in the mouse air pouch model of acute inflammation
Delano, David L; Montesinos, M Carmen; D'Eustachio, Peter; Wiltshire, Tim; Cronstein, Bruce N
2005 Feb;29(1):1-7, Inflammation
The widely used mouse air pouch model of acute inflammation is inducible in a variety of inbred strains, but the potential influence of genetic background and gender on inflammation severity has never been examined. We directly compared the degree of inflammation induced in the air pouch model across four commonly utilized inbred strains in both male and female mice. We then applied an in silico mapping method to identify loci potentially associated with determining inflammation severity for each gender. Air pouches were induced by subcutaneous injection 3 (3 cc) and 5 (1.5 cc) days prior to the experiment. 4h after carrageenan injection, exudates were retrieved and leukocyte concentration quantified using a hemocytometer. The in silico mapping method was applied as described below. The strain order for mean leukocyte count/mL in inflamed exudates differed between genders. In males, the order was C57BL/6J > BALB/cByJ > DBA/2J > DBA/1J, while in females the order was BALB/cByJ > DBA/2J > C57BL/6J > DBA/1J. The difference in inflammation severity between genders reached significance only in C57BL/6J mice. Independent in silico analysis based on phenotypic data from male versus female mice identified distinct sets of loci as potentially associated with the exudate count reached. We conclude that the degree of inflammation induced in the mouse air pouch model of inflammation is strain-specific and, therefore, genetically based, and the pattern of interstrain differences is altered in male relative to female mice. The loci identified by in silico mapping likely contain genes with differential roles in determining this phenotype between genders
— id: 64161, year: 2005, vol: 29, page: 1, stat: Journal Article,

Genetically based resistance to the antiinflammatory effects of methotrexate in the air-pouch model of acute inflammation
Delano, David L; Montesinos, M Carmen; Desai, Avani; Wilder, Tuere; Fernandez, Patricia; D'Eustachio, Peter; Wiltshire, Tim; Cronstein, Bruce N
2005 Aug;52(8):2567-2575, Arthritis & rheumatism
OBJECTIVE: Low-dose methotrexate (MTX), a mainstay in the treatment of rheumatoid arthritis, is effective in only 60-70% of patients, a finding mirrored by poor antiinflammatory efficacy in some animal models, most notably collagen-induced arthritis. To determine whether genetic factors or the model itself is responsible for the poor response to MTX, we directly compared the responses of 4 inbred mouse strains to MTX in the air-pouch model of acute inflammation. METHODS: The exudate leukocyte count and adenosine concentration were determined in inbred mice treated with MTX (0.75 mg/kg intraperitoneally every week for 4 weeks) or vehicle 4 hours after injection of carrageenan into the air pouch using previously described methods. Quantitative trait locus mapping was performed using an in silico, or computer-based, method to identify loci potentially associated with each phenotype. RESULTS: MTX significantly reduced the exudate leukocyte count in C57BL/6J and BALB/cJ mice, but not DBA/1J (the strain used in the collagen-induced arthritis model) or DBA/2J mice. In a parallel manner, MTX increased adenosine concentration in inflammatory exudates of C57BL/6J and BALB/cJ mice, but not DBA/1J or DBA/2J mice. Antiinflammatory and adenosine responses to MTX in DBA/1J x C57BL/6J F(1) and F(2) offspring were most consistent with single genetic loci being responsible for each phenotype. In silico mapping identified partially overlapping loci containing candidate genes involved in both responses. CONCLUSION: Genetic factors contribute to the antiinflammatory efficacy of MTX, and a single locus involved in MTX-induced adenosine up-regulation is likely responsible for the observed resistance to MTX in DBA/1J mice
— id: 57722, year: 2005, vol: 52, page: 2567, stat: Journal Article,

Reactome: a knowledgebase of biological pathways
Joshi-Tope, G; Gillespie, M; Vastrik, I; D'Eustachio, P; Schmidt, E; de Bono, B; Jassal, B; Gopinath, GR; Wu, GR; Matthews, L; Lewis, S; Birney, E; Stein, L
2005 JAN 1 ;33(2):D428-D432, Nucleic acids research
Reactome, located at http://www.reactome.org is a curated, peer-reviewed resource of human biological processes. Given the genetic makeup of an organism, the complete set of possible reactions constitutes its reactome. The basic unit of the Reactome database is a reaction; reactions are then grouped into causal chains to form pathways. The Reactome data model allows us to represent many diverse processes in the human system, including the pathways of intermediary metabolism, regulatory pathways, and signal transduction, and high-level processes, such as the cell cycle. Reactome provides a qualitative framework, on which quantitative data can be superimposed. Tools have been developed to facilitate custom data entry and annotation by expert biologists, and to allow visualization and exploration of the finished dataset as an interactive process map. Although our primary curational domain is pathways from Homo sapiens, we regularly create electronic projections of human pathways onto other organisms via putative orthologs, thus making Reactome relevant to model organism research communities. The database is publicly available under open source terms, which allows both its content and its software infrastructure to be freely used and redistributed
— id: 48673, year: 2005, vol: 33, page: D428, stat: Journal Article,

Genetically-based resistance to methotrexate (MTX) in the air pouch model of acute inflammation
Delano, DL; Montesinos, MC; Desai, A; D'Eustachio, P; Wiltshire, T; Cronstein, BN
2004 SEP ;50(9):S367-S367, Arthritis & rheumatism
— id: 49044, year: 2004, vol: 50, page: S367, stat: Journal Article,

The Genome Knowledgebase: a resource for biologists and bioinformaticists
Joshi-Tope, G; Vastrik, I; Gopinath, G R; Matthews, L; Schmidt, E; Gillespie, M; D'Eustachio, P; Jassal, B; Lewis, S; Wu, G; Birney, E; Stein, L
2003 ;68:237-243, Cold Spring Harbor symposia on quantitative biology
— id: 45001, year: 2003, vol: 68, page: 237, stat: Journal Article,

The Genome Sequence of Caenorhabditis briggsae: A Platform for Comparative Genomics
Stein, Lincoln D; Bao, Zhirong; Blasiar, Darin; Blumenthal, Thomas; Brent, Michael R; Chen, Nansheng; Chinwalla, Asif; Clarke, Laura; Clee, Chris; Coghlan, Avril; Coulson, Alan; D'Eustachio, Peter; Fitch, David H A; Fulton, Lucinda A; Fulton, Robert E; Griffiths-Jones, Sam; Harris, Todd W; Hillier, LaDeana W; Kamath, Ravi; Kuwabara, Patricia E; Mardis, Elaine R; Marra, Marco A; Miner, Tracie L; Minx, Patrick; Mullikin, James C; Plumb, Robert W; Rogers, Jane; Schein, Jacqueline E; Sohrmann, Marc; Spieth, John; Stajich, Jason E; Wei, C; Willey, David; Wilson, Richard K; Durbin, Richard; Waterston, Robert H
2003 Nov;1(2):E45-E45, PLoS biology
The soil nematodes Caenorhabditis briggsae and Caenorhabditis elegans diverged from a common ancestor roughly 100 million years ago and yet are almost indistinguishable by eye. They have the same chromosome number and genome sizes, and they occupy the same ecological niche. To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence. We predict approximately 19,500 protein-coding genes in the C. briggsae genome, roughly the same as in C. elegans. Of these, 12,200 have clear C. elegans orthologs, a further 6,500 have one or more clearly detectable C. elegans homologs, and approximately 800 C. briggsae genes have no detectable matches in C. elegans. Almost all of the noncoding RNAs (ncRNAs) known are shared between the two species. The two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers. Operons, a distinctive feature of C. elegans, are highly conserved in C. briggsae, with the arrangement of genes being preserved in 96% of cases. The difference in size between the C. briggsae (estimated at approximately 104 Mbp) and C. elegans (100.3 Mbp) genomes is almost entirely due to repetitive sequence, which accounts for 22.4% of the C. briggsae genome in contrast to 16.5% of the C. elegans genome. Few, if any, repeat families are shared, suggesting that most were acquired after the two species diverged or are undergoing rapid evolution. Coclustering the C. elegans and C. briggsae proteins reveals 2,169 protein families of two or more members. Most of these are shared between the two species, but some appear to be expanding or contracting, and there seem to be as many as several hundred novel C. briggsae gene families. The C. briggsae draft sequence will greatly improve the annotation of the C. elegans genome. Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes. In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes
— id: 45002, year: 2003, vol: 1, page: E45, stat: Journal Article,

High levels of mitochondrial DNA heteroplasmy in human hairs by Budowle et al
D'Eustachio, Peter
2002 Nov 5;130(1):63-67, Forensic science international
— id: 45003, year: 2002, vol: 130, page: 63, stat: Journal Article,

Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease
Hou, XY; Mrug, M; Yoder, BK; Lefkowitz, EJ; Kremmidiotis, G; D'Eustachio, P; Beier, DR; Guay-Woodford, LM
2002 Feb;109(4):533-540, Journal of clinical investigation
The congenital polycystic kidney (cpk) mutation is the most extensively characterized mouse model of polycystic kidney disease (PKD). The renal cystic disease is fully expressed in homozygotes and is strikingly similar to human autosomal recessive PKD (ARPKD), whereas genetic background modulates the penetrance of the corresponding defect in the developing biliary tree. We now describe the positional cloning, mutation analysis, and expression of a novel gene that is disrupted in cpk mice. The cpk gene is expressed primarily in the kidney and liver and encodes a hydrophilic, 145-amino acid protein, which we term cystin. When expressed exogenously in polarized renal epithelial cells, cystin is detected in cilia, and its expression overlaps with polaris, another PKD-related protein. We therefore propose that the single epithelial cilium is important in the functional differentiation of polarized epithelia and that ciliary dysfunction underlies the PKD phenotype in cpk mice
— id: 27550, year: 2002, vol: 109, page: 533, stat: Journal Article,

The small GTPase Ran
D'Eustachio, Peter; Rush, Mark G.
Boston : Kluwer Academic, c2001,
— id: 730, year: 2001, vol: , page: , stat: ,

Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding
Michaelson D; Silletti J; Murphy G; D'Eustachio P; Rush M; Philips MR
2001 Jan 8;152(1):111-126, Journal of cell biology
Determinants of membrane targeting of Rho proteins were investigated in live cells with green fluorescent fusion proteins expressed with or without Rho-guanine nucleotide dissociation inhibitor (GDI)alpha. The hypervariable region determined to which membrane compartment each protein was targeted. Targeting was regulated by binding to RhoGDI alpha in the case of RhoA, Rac1, Rac2, and Cdc42hs but not RhoB or TC10. Although RhoB localized to the plasma membrane (PM), Golgi, and motile peri-Golgi vesicles, TC10 localized to PMs and endosomes. Inhibition of palmitoylation mislocalized H-Ras, RhoB, and TC10 to the endoplasmic reticulum. Although overexpressed Cdc42hs and Rac2 were observed predominantly on endomembrane, Rac1 was predominantly at the PM. RhoA was cytosolic even when expressed at levels in vast excess of RhoGDI alpha. Oncogenic Dbl stimulated translocation of green fluorescent protein (GFP)-Rac1, GFP-Cdc42hs, and GFP-RhoA to lamellipodia. RhoGDI binding to GFP-Cdc42hs was not affected by substituting farnesylation for geranylgeranylation. A palmitoylation site inserted into RhoA blocked RhoGDI alpha binding. Mutations that render RhoA, Cdc42hs, or Rac1, either constitutively active or dominant negative abrogated binding to RhoGDI alpha and redirected expression to both PMs and internal membranes. Thus, despite the common essential feature of the CAAX (prenylation, AAX tripeptide proteolysis, and carboxyl methylation) motif, the subcellular localizations of Rho GTPases, like their functions, are diverse and dynamic
— id: 17229, year: 2001, vol: 152, page: 111, stat: Journal Article,

An integrated genetic and physical map of the 650-kb region containing the congenital polycystic kidney (cpk) locus on mouse Chromosome 12
Mrug, M; Green, WJ; Dasgupta, S; Beier, DR; Lu, W; D'Eustachio, P; Guay-Woodford, LM
2001 Nov;94(1-2):55-61, Cytogenetics & cell genetics
Mice homozygous for the congenital polycystic kidney (cpk) mutation develop a rapidly progressive form of polycystic kidney disease. We report an integrated genetic and physical map of the 650-kb region containing the cpk locus and the exclusion of Rrm2 and Idb2 as candidate cpk genes. Our study establishes the requisite foundation for positional cloning of the cpk gene.
— id: 28205, year: 2001, vol: 94, page: 55, stat: Journal Article,

Signaling mediated by the closely related mammalian Rho family GTPases TC10 and Cdc42 suggests distinct functional pathways
Murphy GA; Jillian SA; Michaelson D; Philips MR; D'Eustachio P; Rush MG
2001 Mar;12(3):157-167, Cell growth & differentiation
The mammalian Rho family GTPases TC10 and Cdc42 share many properties. Activated forms of both proteins stimulate transcription mediated by nuclear factor kappaB, serum response factor, and the cyclin D1 promoter; activate c-Jun NH2-terminal kinase; cooperate with activated Raf to transform NIH-3T3 cells; and, by a mechanism independent of all of these effects, induce filopodia formation. In contrast, previously reported differences between TC10 and Cdc42 are not striking. We now present studies of TC10 and Cdc42 in cell culture that reveal clear functional differences: (a) wild-type TC10 localizes predominantly to the plasma membrane and less extensively to a perinuclear membranous compartment, whereas wild-type Cdc42 localizes predominantly to this compartment and less extensively to the plasma membrane; (b) expression of Rho guanine nucleotide dissociation inhibitor alpha results in a redistribution of wild-type Cdc42 to the cytosol but has no effect on the plasma membrane localization of wild-type TC10; (c) TC10 fails to rescue a Saccharomyces cerevisiae cdc42 mutation, unlike mammalian Cdc42; (d) dominant negative Cdc42, but not dominant negative TC10, inhibits neurite outgrowth in PC12 cells stimulated by nerve growth factor; and (e) activation of nuclear factor kappaB-dependent transcription by Cdc42, but not by TC10, is inhibited by sodium salicylate. These findings point to distinct pathways in which TC10 and Cdc42 may act and distinct modes of regulation of these proteins
— id: 26749, year: 2001, vol: 12, page: 157, stat: Journal Article,

Mouse chromosome 12
D'Eustachio, P; Riblet, R
2000 NOV ;11(11):953-953, Mammalian genome
— id: 54472, year: 2000, vol: 11, page: 953, stat: Journal Article,

Mouse chromosome 12
D'Eustachio P; Riblet R
1999 Oct;10(10):953-953, Mammalian genome
— id: 11955, year: 1999, vol: 10, page: 953, stat: Journal Article,

Differential localization of rho GTPases: Dominant negative alleles cannot bind rhoGDI
Michaelson, D; Murphy, GA; Rush, MG; D'Eustachio, P; Philips, MR
1999 NOV ;10(5):90A-90A, Molecular biology of the cell
— id: 53778, year: 1999, vol: 10, page: 90A, stat: Journal Article,

Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth
Murphy GA; Solski PA; Jillian SA; Perez de la Ossa P; D'Eustachio P; Der CJ; Rush MG
1999 Jul 1;18(26):3831-3845, Oncogene
The small Ras-related GTPase, TC10, has been classified on the basis of sequence homology to be a member of the Rho family. This family, which includes the Rho, Rac and CDC42 subfamilies, has been shown to regulate a variety of apparently diverse cellular processes such as actin cytoskeletal organization, mitogen-activated protein kinase (MAPK) cascades, cell cycle progression and transformation. In order to begin a study of TC10 biological function, we expressed wild type and various mutant forms of this protein in mammalian cells and investigated both the intracellular localization of the expressed proteins and their abilities to stimulate known Rho family-associated processes. Wild type TC10 was located predominantly in the cell membrane (apparently in the same regions as actin filaments), GTPase defective (75L) and GTP-binding defective (31N) mutants were located predominantly in cytoplasmic perinuclear regions, and a deletion mutant lacking the carboxyl terminal residues required for post-translational prenylation was located predominantly in the nucleus. The GTPase defective (constitutively active) TC10 mutant: (1) stimulated the formation of long filopodia; (2) activated c-Jun amino terminal kinase (JNK); (3) activated serum response factor (SRF)-dependent transcription; (4) activated NF-kappaB-dependent transcription; and (5) synergized with an activated Raf-kinase (Raf-CAAX) to transform NIH3T3 cells. In addition, wild type TC10 function is required for full H-Ras transforming potential. We demonstrate that an intact effector domain and carboxyl terminal prenylation signal are required for proper TC10 function and that TC10 signals to at least two separable downstream target pathways. In addition, TC10 interacted with the actin-binding and filament-forming protein, profilin, in both a two-hybrid cDNA library screen, and an in vitro binding assay. Taken together, these data support a classification of TC10 as a member of the Rho family, and in particular, suggest that TC10 functions to regulate cellular signaling to the actin cytoskeleton and processes associated with cell growth
— id: 7968, year: 1999, vol: 18, page: 3831, stat: Journal Article,

Isolated mammalian and Schizosaccharomyces pombe ran-binding domains rescue S. pombe sbp1 (RanBP1) genomic mutants
Novoa I; Rush MG; D'Eustachio P
1999 Jul;10(7):2175-2190, Molecular biology of the cell
Mammalian Ran-binding protein-1 (RanBP1) and its fission yeast homologue, sbp1p, are cytosolic proteins that interact with the GTP-charged form of Ran GTPase through a conserved Ran-binding domain (RBD). In vitro, this interaction can accelerate the Ran GTPase-activating protein-mediated hydrolysis of GTP on Ran and the turnover of nuclear import and export complexes. To analyze RanBP1 function in vivo, we expressed exogenous RanBP1, sbp1p, and the RBD of each in mammalian cells, in wild-type fission yeast, and in yeast whose endogenous sbp1 gene was disrupted. Mammalian cells and wild-type yeast expressing moderate levels of each protein were viable and displayed normal nuclear protein import. sbp1(-) yeast were inviable but could be rescued by all four exogenous proteins. Two RBDs of the mammalian nucleoporin RanBP2 also rescued sbp1(-) yeast. In mammalian cells, wild-type yeast, and rescued mutant yeast, exogenous full-length RanBP1 and sbp1p localized predominantly to the cytosol, whereas exogenous RBDs localized predominantly to the cell nucleus. These results suggest that only the RBD of sbp1p is required for its function in fission yeast, and that this function may not require confinement of the RBD to the cytosol. The results also indicate that the polar amino-terminal portion of sbp1p mediates cytosolic localization of the protein in both yeast and mammalian cells
— id: 8487, year: 1999, vol: 10, page: 2175, stat: Journal Article,

Essential role of STAT3 for embryonic stem cell pluripotency
Raz R; Lee CK; Cannizzaro LA; d'Eustachio P; Levy DE
1999 Mar 16;96(6):2846-2851, Proceedings of the National Academy of Sciences of the United States of America
Propagation of mouse embryonic stem (ES) cells in vitro requires exogenous leukemia inhibitory factor (LIF) or related cytokines. Potential downstream effectors of the LIF signal in ES cells include kinases of the Src, Jak, and mitogen-activated protein families and the signal transducer and transcriptional activator STAT3. Activation of nuclear STAT3 and the ability of ES cells to grow as undifferentiated clones were monitored during LIF withdrawal. A correlation was found between levels of STAT3 activity and maintenance of an undifferentiated phenotype at clonal density. In contrast, variation in STAT3 activity did not affect cell proliferation. The requirement for STAT3 was analyzed by targeted mutagenesis in ES cell lines exhibiting different degrees of LIF dependency. An insertional mutation was devised that abrogated Stat3 gene expression but could be reversed by Cre recombination-mediated excision. ES cells heterozygous for the Stat3 mutation could be isolated only from E14 cells, the line least dependent on LIF for self-renewal. Targeted clones isolated from other ES cell lines were invariably trisomic for chromosome 11, which carries the Stat3 locus, and retained normal levels of activated STAT3. Cre-regulated reduction of Stat3 gene copy number in targeted, euploid E14 clones resulted in dose-dependent losses of STAT3 activity and the efficiency of self-renewal without commensurate changes in cell cycle progression. These results demonstrate an essential role for a critical amount of STAT3 in the maintenance of an undifferentiated ES cell phenotype
— id: 8219, year: 1999, vol: 96, page: 2846, stat: Journal Article,

Encyclopedia of the mouse genome VII. Mouse chromosome 12
D'Eustachio P; Riblet R
1998 ;8 Spec No:S241-S257, Mammalian genome
— id: 12097, year: 1998, vol: 8 Spec No, page: S241, stat: Journal Article,

Cellular functions of TC10, a Rho family GTPase: Regulation of morphology, signal transduction, and cell division
Murphy, GA; Solski, P; de la Ossa, PP; D'Eustachio, P; Der, CJ; Rush, MG
1998 NOV ;9(11):117A-117A, Molecular biology of the cell
— id: 53643, year: 1998, vol: 9, page: 117A, stat: Journal Article,

Essential role of STAT3 for embryonic stem cell growth
Raz, R; D'Eustachio, P; Kennizzaro, L; Levy, DE
1998 SEP ;9(3):328-328, European cytokine network
— id: 53660, year: 1998, vol: 9, page: 328, stat: Journal Article,

Mouse chromosome 12
D'Eustachio P; Riblet R
1997 ;7 Spec No:S209-S222, Mammalian genome
— id: 12406, year: 1997, vol: 7 Spec No, page: S209, stat: Journal Article,

A T42A Ran mutation: differential interactions with effectors and regulators, and defect in nuclear protein import
Murphy GA; Moore MS; Drivas G; Perez de la Ossa P; Villamarin A; D'Eustachio P; Rush MG
1997 Dec;8(12):2591-2604, Molecular biology of the cell
Ran, the small, predominantly nuclear GTPase, has been implicated in the regulation of a variety of cellular processes including cell cycle progression, nuclear-cytoplasmic trafficking of RNA and protein, nuclear structure, and DNA synthesis. It is not known whether Ran functions directly in each process or whether many of its roles may be secondary to a direct role in only one, for example, nuclear protein import. To identify biochemical links between Ran and its functional target(s), we have generated and examined the properties of a putative Ran effector mutation, T42A-Ran. T42A-Ran binds guanine nucleotides as well as wild-type Ran and responds as well as wild-type Ran to GTP or GDP exchange stimulated by the Ran-specific guanine nucleotide exchange factor, RCC1. T42A-Ran.GDP also retains the ability to bind p10/NTF2, a component of the nuclear import pathway. In contrast to wild-type Ran, T42A-Ran.GTP binds very weakly or not detectably to three proposed Ran effectors, Ran-binding protein 1 (RanBP1), Ran-binding protein 2 (RanBP2, a nucleoporin), and karyopherin beta (a component of the nuclear protein import pathway), and is not stimulated to hydrolyze bound GTP by Ran GTPase-activating protein, RanGAP1. Also in contrast to wild-type Ran, T42A-Ran does not stimulate nuclear protein import in a digitonin permeabilized cell assay and also inhibits wild-type Ran function in this system. However, the T42A mutation does not block the docking of karyophilic substrates at the nuclear pore. These properties of T42A-Ran are consistent with its classification as an effector mutant and define the exposed region of Ran containing the mutation as a probable effector loop
— id: 12209, year: 1997, vol: 8, page: 2591, stat: Journal Article,

The Mtv29 gene encoding endogenous lymphoma superantigen in SJL mice, mapped to proximal chromosome 6
Zhang DJ; D'Eustachio P; Thorbecke GJ
1997 ;46(2):163-166, Immunogenetics
— id: 7957, year: 1997, vol: 46, page: 163, stat: Journal Article,

Encyclopedia of the mouse genome V. Mouse chromosome 12
D'Eustachio P; Riblet R
1996 ;6 Spec No:S221-S231, Mammalian genome
— id: 12685, year: 1996, vol: 6 Spec No, page: S221, stat: Journal Article,

Mouse Chromosome 12
D'Eustachio P; Riblet R
1996 ;6(13):221-231, Mammalian genome
— id: 12695, year: 1996, vol: 6, page: 221, stat: Journal Article,

Evidence that two phenotypically distinct mouse PKD mutations, bpk and jcpk, are allelic
Guay-Woodford LM; Bryda EC; Christine B; Lindsey JR; Collier WR; Avner ED; D'Eustachio P; Flaherty L
1996 Oct;50(4):1158-1165, Kidney international
Numerous mouse models of polycystic kidney disease (PKD) have been described. All of these diseases are transmitted as single recessive traits and in most, the phenotypic severity is influenced by the genetic background. However, based on their genetic map positions, none of these loci appears to be allelic and none are candidate modifier loci for any other mouse PKD mutation. Previously, we have described the mouse bpk mutation, a model that closely resembles human autosomal recessive polycystic kidney disease. We now report that the bpk mutation maps to a 1.6 CM interval on mouse Chromosome 10, and that the renal cystic disease severity in our intersubspecific intercross progeny is influenced by the genetic background. Interestingly, bpk co-localizes with jcpk, a phenotypically-distinct PKD mutation, and complementation testing indicates that the bpk and jcpk mutations are allelic. These data imply that distinct PKD phenotypes can result from different mutations within a single gene. In addition, based on its map position, the bpk locus is a candidate genetic modifier for jck, a third phenotypically-distinct PKD mutation
— id: 17230, year: 1996, vol: 50, page: 1158, stat: Journal Article,

The small nuclear GTPase Ran: how much does it run?
Rush MG; Drivas G; D'Eustachio P
1996 Feb;18(2):103-112, Bioessays
Ran is one of the most abundant and best conserved of the small GTP binding and hydrolyzing proteins of eukaryotes. It is located predominantly in cell nuclei. Ran is a member of the Ras family of GTPases, which includes the Ras and Ras-like proteins that regulate cell growth and division, the Rho and Rac proteins that regulate cytoskeletal organization and the Rab proteins that regulate vesicular sorting. Ran differs most obviously from other members of the Ras family in both its nuclear localization, and its lack of sites required for post-translational lipid modification. Ran is, however, similar to other Ras family members in requiring a specific guanine nucleotide exchange factor (GEF) and a specific GTPase activating protein (GAP) as stimulators of overall GTPase activity. In this review, the multiple cellular functions of Ran are evaluated with respect to its known biochemistry and molecular interactions
— id: 12650, year: 1996, vol: 18, page: 103, stat: Journal Article,

Separate domains of the Ran GTPase interact with different factors to regulate nuclear protein import and RNA processing
Ren M; Villamarin A; Shih A; Coutavas E; Moore MS; LoCurcio M; Clarke V; Oppenheim JD; D'Eustachio P; Rush MG
1995 Apr;15(4):2117-2124, Molecular & cellular biology
The small Ras-related GTP binding and hydrolyzing protein Ran has been implicated in a variety of processes, including cell cycle progression, DNA synthesis, RNA processing, and nuclear-cytosolic trafficking of both RNA and proteins. Like other small GTPases, Ran appears to function as a switch: Ran-GTP and Ran-GDP levels are regulated both by guanine nucleotide exchange factors and GTPase activating proteins, and Ran-GTP and Ran-GDP interact differentially with one or more effectors. One such putative effector, Ran-binding protein 1 (RanBP1), interacts selectively with Ran-GTP. Ran proteins contain a diagnostic short, acidic, carboxyl-terminal domain, DEDDDL, which, at least in the case of human Ran, is required for its role in cell cycle regulation. We show here that this domain is required for the interaction between Ran and RanBP1 but not for the interaction between Ran and a Ran guanine nucleotide exchange factor or between Ran and a Ran GTPase activating protein. In addition, Ran lacking this carboxyl-terminal domain functions normally in an in vitro nuclear protein import assay. We also show that RanBP1 interacts with the mammalian homolog of yeast protein RNA1, a protein involved in RNA transport and processing. These results are consistent with the hypothesis that Ran functions directly in at least two pathways, one, dependent on RanBP1, that affects cell cycle progression and RNA export, and another, independent of RanBP1, that affects nuclear protein import
— id: 6723, year: 1995, vol: 15, page: 2117, stat: Journal Article,

Cloning of neurotrimin defines a new subfamily of differentially expressed neural cell adhesion molecules
Struyk AF; Canoll PD; Wolfgang MJ; Rosen CL; D'Eustachio P; Salzer JL
1995 Mar;15(3 Pt 2):2141-2156, Journal of neuroscience
Previous studies in the laboratory indicated that glycosylphosphatidylinositol (GPI)-anchored proteins may generate diversity of the cell surface of different neuronal populations (Rosen et al., 1992). In this study, we have extended these findings and surveyed the expression of GPI-anchored proteins in the developing rat CNS. In addition to several well characterized GPI-anchored cell adhesion molecules (CAMs), we detected an unidentified broad band of 65 kDa that is the earliest and most abundantly expressed GPI-anchored species in the rat CNS. Purification of this protein band revealed that it is comprised of several related proteins that define a novel subfamily of immunoglobulin-like (Ig) CAMs. One of these proteins is the opiate binding-cell adhesion molecule (OBCAM). We have isolated a cDNA encoding a second member of this family, that we have termed neurotrimin, and present evidence for the existence of additional family members. Like OBCAM, with which it shares extensive sequence identity, neurotrimin contains three immunoglobulin-like domains. Both proteins are encoded by distinct genes that may be clustered on the proximal end of mouse chromosome 9. Characterization of the expression of neurotrimin and OBCAM in the developing CNS by in situ hybridization reveals that these proteins are differentially expressed during development. Neurotrimin is expressed at high levels in several developing projection systems: in neurons of the thalamus, subplate, and lower cortical laminae in the forebrain and in the pontine nucleus, cerebellar granule cells, and Purkinje cells in the hindbrain. Neurotrimin is also expressed at high levels in the olfactory bulb, neural retina, dorsal root ganglia, spinal cord, and in a graded distribution in the basal ganglia and hippocampus. OBCAM has a much more restricted distribution, being expressed at high levels principally in the cortical plate and hippocampus. These results suggest that these proteins, together with other members of this family, provide diversity to the surfaces of different neuronal populations that could be important in the specification of neuronal connectivity
— id: 6757, year: 1995, vol: 15, page: 2141, stat: Journal Article,

Tissue-specific expression of Ran isoforms in the mouse
Coutavas EE; Hsieh CM; Ren M; Drivas GT; Rush MG; D'Eustachio PD
1994 Oct;5(10):623-628, Mammalian genome
Ran genes encode a family of well-conserve small nuclear GTPases (Ras-related nuclear proteins), whose function is implicated in both normal cell cycle progression and the transport of RNA and proteins between the nucleus and the cytoplasm. Previous studies of Ran proteins have utilized cell-free systems, yeasts, and cultured mammalian cells. We have now characterized patterns of Ran gene expression in the mouse. Serum starvation suppressed Ran gene transcription in mouse 3T3 cells. Ran mRNA reappeared in cells within 3 h after refeeding. A single Ran mRNA species was detected at low levels in most somatic tissues of the adult mouse. In testis, this Ran mRNA was abundant, as were other larger transcripts. Analysis of testis-derived Ran cDNA clones revealed the presence of two transcripts, one specifying an amino acid sequence identical to that of human Ran/TC4 and one specifying an amino acid sequence 94% identical. Northern blotting and reverse transcriptase-PCR assays with oligonucleotide probes and primers specific for each transcript demonstrated that the isoform identical to Ran/TC4 was expressed in both somatic tissues and testis, while the variant form was transcribed only in testis. The existence of tissue-specific Ran isoforms may help to rationalize the diverse roles suggested for Ran by previous biochemical studies
— id: 56625, year: 1994, vol: 5, page: 623, stat: Journal Article,

Mouse chromosome 12
D'Eustachio P
1994 ;5 Spec No:S181-S195, Mammalian genome
— id: 13039, year: 1994, vol: 5 Spec No, page: S181, stat: Journal Article,

Aberrant function of the Ras-related protein TC21/R-Ras2 triggers malignant transformation
Graham SM; Cox AD; Drivas G; Rush MG; D'Eustachio P; Der CJ
1994 Jun;14(6):4108-4115, Molecular & cellular biology
Although the human Ras proteins are members of a large superfamily of Ras-related proteins, to date, only the proteins encoded by the three mammalian ras genes have been found to possess oncogenic potential. Among the known Ras-related proteins, TC21/R-Ras2 exhibits the most significant amino acid identity (55%) to Ras proteins. We have generated mutant forms of TC21 that possess amino acid substitutions analogous to those that activate Ras oncogenic potential [designated TC21(22V) and TC21(71L)] and compared the biological properties of TC21 with those of Ras proteins in NIH 3T3 and Rat-1 transformation assays. Whereas wild-type TC21 did not show any transforming potential in vitro, both TC21(22V) and TC21(71L) displayed surprisingly potent transforming activities that were comparable to the strong transforming activity of oncogenic Ras proteins. Like Ras-transformed cells, NIH 3T3 cells expressing mutant TC21 proteins formed foci of morphologically transformed cells in monolayer cultures, proliferated in low serum, formed colonies in soft agar, and developed progressive tumors in nude mice. Thus, TC21 is the first Ras-related protein to exhibit potent transforming activity equivalent to that of Ras. Furthermore, mutant TC21 proteins also stimulated constitutive activation of mitogen-activated protein kinases as well as transcriptional activation from Ras-responsive promoter elements (Ets/AP-1 and NF-kappa B). We conclude that aberrant TC21 function may trigger cellular transformation via a signal transduction pathway similar to that of oncogenic Ras and suggest that deregulated TC21 activity may contribute significantly to human oncogenesis
— id: 17231, year: 1994, vol: 14, page: 4108, stat: Journal Article,

Identification of a simple sequence polymorphism within the mouse locus D12Nyu2
Guay-Woodford LM; Bruns GA; D'Eustachio P
1994 Apr;5(4):251-252, Mammalian genome
— id: 17233, year: 1994, vol: 5, page: 251, stat: Journal Article,

Refinement of the DNA marker maps of mouse chromosome 12
Khan F; Clarke V; D'Eustachio P
1994 May 1;21(1):128-137, Genomics
To refine the linkage map of mouse Chromosome (Chr) 12 and to define better the homology relationships between it and human chrs 2p and 14q, nine new anonymous DNA markers of Chr 12 were identified, and mouse loci homologous to the human D14S17, CHGA, HSPA2, RRM2, TPO, and ZFP50 ('KUP') genes were defined. The inheritance of DNA variants associated with these markers was followed in progeny of a reciprocal backcross between the C57BL/6J and SWR/J laboratory mouse strains and in recombinant inbred (RI) strains of mice. These data, combined with results of previous analyses of the backcross, allowed the construction of a 22-marker multilocus linkage map that spanned 58 cM. Use of this map to anchor the RI typing data collected in this and previous studies allowed the construction of a 79-marker map that spanned 66 cM and the identification of a framework of unambiguously ordered, extensively typed markers that should facilitate the use of RI mice in testing new markers for possible linkage to Chr 12
— id: 6420, year: 1994, vol: 21, page: 128, stat: Journal Article,

Effects of mutant Ran/TC4 proteins on cell cycle progression
Ren M; Coutavas E; D'Eustachio P; Rush MG
1994 Jun;14(6):4216-4224, Molecular & cellular biology
Ran/TC4, a member of the RAS gene superfamily, encodes an abundant nuclear protein that binds and hydrolyzes GTP. Transient expression of a Ran/TC4 mutant protein deficient in GTP hydrolysis blocked DNA replication, suggesting a role for Ran/TC4 in the regulation of cell cycle progression. To test this possibility, we exploited an efficient transfection system, involving the introduction of cDNAs in the pMT2 vector into 293/Tag cells, to analyze phenotypes associated with mutant and wild-type Ran/TC4 expression. Expression of a Ran/TC4 mutant protein deficient in GTP hydrolysis inhibited proliferation of transfected cells by arresting them predominantly in the G2, but also in the G1, phase of the cell cycle. Deletion of an acidic carboxy-terminal hexapeptide from the Ran/TC4 mutant did not alter its nuclear localization but did block its inhibitory effect on cell cycle progression. These data suggest that normal progression of the cell cycle is coupled to the operation of a Ran/TC4 GTPase cycle. Mediators of this coupling are likely to include the nuclear regulator of chromosome condensation 1 protein and the mitosis-promoting factor complex
— id: 6494, year: 1994, vol: 14, page: 4216, stat: Journal Article,

The mouse congenital polycystic kidney (cpk) locus maps within 1.3 cM of the chromosome 12 marker D12Nyu2
Simon EA; Cook S; Davisson MT; D'Eustachio P; Guay-Woodford LM
1994 May 15;21(2):415-418, Genomics
The mouse congenital polycystic kidney (cpk) mutation causes bilateral cystic dilatation of the renal collecting tubules and leads to rapidly progressive renal insufficiency in affected homozygotes. The phenotype of the cpk/cpk mutants closely resembles that of human autosomal recessive polycystic kidney disease (ARPKD). Previously, we have reported that the cpk locus maps close to D12Nyu2 on Chromosome (Chr) 12. To determine the cpk map location more precisely, we have extended our previous studies using additional progeny and additional markers of proximal Chr 12. These recent studies position cpk within 1.3 cM of D12Nyu2, closely flanked by (Odc, D12Mit10) and (Tpo, D12Mit12). Our data support an ordered array of seven DNA markers that will provide reference points for building a physical map of the Chr 12 region centered on cpk. Moreover, these data establish that cpk lies within a linkage group that is conserved between mouse Chr 12 and human chr 2p24-2p25. This assignment to a region of homology will facilitate human linkage analyses to determine whether mouse cpk and human ARPKD are mutations of homologous genes
— id: 17232, year: 1994, vol: 21, page: 415, stat: Journal Article,

The SH2 domain protein GRB-7 is co-amplified, overexpressed and in a tight complex with HER2 in breast cancer
Stein D; Wu J; Fuqua SA; Roonprapunt C; Yajnik V; D'Eustachio P; Moskow JJ; Buchberg AM; Osborne CK; Margolis B
1994 Mar 15;13(6):1331-1340, EMBO journal
SH2 domain proteins are important components of the signal transduction pathways activated by growth factor receptor tyrosine kinases. We have been cloning SH2 domain proteins by bacterial expression cloning using the tyrosine phosphorylated C-terminus of the epidermal growth factor receptor as a probe. One of these newly cloned SH2 domain proteins, GRB-7, was mapped on mouse chromosome 11 to a region which also contains the tyrosine kinase receptor, HER2/erbB-2. The analogous chromosomal locus in man is often amplified in human breast cancer leading to overexpression of HER2. We find that GRB-7 is amplified in concert with HER2 in several breast cancer cell lines and that GRB-7 is overexpressed in both cell lines and breast tumors. GRB-7, through its SH2 domain, binds tightly to HER2 such that a large fraction of the tyrosine phosphorylated HER2 in SKBR-3 cells is bound to GRB-7. GRB-7 can also bind tyrosine phosphorylated SHC, albeit at a lower affinity than GRB2 binds SHC. We also find that GRB-7 has a strong similarity over > 300 amino acids to a newly identified gene in Caenorhabditis elegans. This region of similarity, which lies outside the SH2 domain, also contains a pleckstrin homology domain. The presence of evolutionarily conserved domains indicates that GRB-7 is likely to perform a basic signaling function. The fact that GRB-7 and HER2 are both overexpressed and bound tightly together suggests that this basic signaling pathway is greatly amplified in certain breast cancers
— id: 6528, year: 1994, vol: 13, page: 1331, stat: Journal Article,

Refined localization of H7 and Ctt1 on distal mouse chromosome 9
Vagliani M; D'Eustachio P; Colombo MP
1994 ;40(1):79-81, Immunogenetics
— id: 17234, year: 1994, vol: 40, page: 79, stat: Journal Article,

Identification of a carbonic anhydrase-like domain in the extracellular region of RPTP gamma defines a new subfamily of receptor tyrosine phosphatases
Barnea G; Silvennoinen O; Shaanan B; Honegger AM; Canoll PD; D'Eustachio P; Morse B; Levy JB; Laforgia S; Huebner K; et al
1993 Mar;13(3):1497-1506, Molecular & cellular biology
The tyrosine phosphatase RPTP gamma is a candidate tumor suppressor gene since it is located on human chromosome 3p14.2-p21 in a region frequently deleted in certain types of renal and lung carcinomas. In order to evaluate its oncogenic potential and to explore its normal in vivo functions, we have isolated cDNAs and deduced the complete sequences of both human and murine RPTP gamma. The murine RPTP gamma gene has been localized to chromosome 14 to a region syntenic to the location of the human gene. Northern (RNA) blot analysis reveals the presence of two major transcripts of 5.5 and 8.5 kb in a variety of murine tissues. In situ hybridization analysis reveals that RPTP gamma mRNA is expressed in specific regions of the brain and that the localization of RPTP gamma changes during brain development. RPTP gamma is composed of a putative extracellular domain, a single transmembrane domain, and a cytoplasmic portion with two tandem catalytic tyrosine phosphatase domains. The extracellular domain contains a stretch of 266 amino acids with striking homology to the zinc-containing enzyme carbonic anhydrase (CAH), indicating that RPTP gamma and RPTP beta (HPTP zeta) represent a subfamily of receptor tyrosine phosphatases. We have constructed a model for the CAH-like domain of RPTP gamma based upon the crystal structure of CAH. It appears that 11 of the 19 residues that form the active site of CAH are conserved in RPTP gamma. Yet only one of the three His residues that ligate the zinc atom and are required for catalytic activity is conserved. On the basis of this model we propose that the CAH-like domain of RPTP gamma may have a function other than catalysis of hydration of metabolic CO2
— id: 13241, year: 1993, vol: 13, page: 1497, stat: Journal Article,

Characterization of proteins that interact with the cell-cycle regulatory protein Ran/TC4
Coutavas E; Ren M; Oppenheim JD; D'Eustachio P; Rush MG
1993 Dec 9;366(6455):585-587, Nature
The human Ras-related nuclear protein Ran/TC4 (refs 1-4) is the prototype of a well conserved family of GTPases that can regulate both cell-cycle progression and messenger RNA transport. Ran has been proposed to undergo tightly controlled cycles of GTP binding and hydrolysis, to operate as a GTPase switch whose GTP- and GDP-bound forms interact differentially with regulators and effectors. One known regulator, the protein RCC1 (refs 12, 13), interacts with Ran to catalyse guanine nucleotide exchange, and both RCC1 and Ran are components of an intrinsic checkpoint control that prevents the premature initiation of mitosis. To test and extend the GTPase-switch model, we searched for a Ran-specific GTPase-activating protein (GAP), and for putative effectors (proteins that interact specifically with Ran/TC4-GTP). We report here the identification of a Ran GAP and its use to characterize the GTP-hydrolysing properties of mutant Ran proteins, and the identification and cloning of a binding protein specific for Ran/TC4-GTP
— id: 6344, year: 1993, vol: 366, page: 585, stat: Journal Article,

Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 12
D'Eustachio P
1993 ;4 Spec No:S176-S191, Mammalian genome
— id: 6351, year: 1993, vol: 4 Spec No, page: S176, stat: Journal Article,

Localization of the twitcher (twi) mutation on mouse chromosome 12
D'Eustachio P; Clarke V
1993 Nov;4(11):684-686, Mammalian genome
— id: 6350, year: 1993, vol: 4, page: 684, stat: Journal Article,

Resolution of the staggerer (sg) mutation from the neural cell adhesion molecule locus (Ncam) on mouse chromosome 9
D'Eustachio P; Davisson MT
1993 ;4(5):278-280, Mammalian genome
— id: 13285, year: 1993, vol: 4, page: 278, stat: Journal Article,

Localization of Shaw-related K+ channel genes on mouse and human chromosomes
Haas M; Ward DC; Lee J; Roses AD; Clarke V; D'Eustachio P; Lau D; Vega-Saenz de Miera E; Rudy B
1993 Dec;4(12):711-715, Mammalian genome
Four related genes, Shaker, Shab, Shaw, and Shal, encode voltage-gated K+ channels in Drosophila. Multigene subfamilies corresponding to each of these Drosophila genes have been identified in rodents and primates; this suggests that the four genes are older than the common ancestor of present-day insects and mammals and that the expansion of each into a family occurred before the divergence of rodents and primates. In order to define these evolutionary relationships more precisely and to facilitate the search for mammalian candidate K+ channel gene mutations, we have mapped members of the Shaw-homologous gene family in humans and mice. Fluorescence in situ hybridization analysis of human metaphase chromosomes mapped KCNC2 (KShIIIA, KV3.2) and KCNC3 (KShIIID, KV3.3) to Chromosome (Chr) 19q13.3-q13.4. Inheritance patterns of DNA restriction fragment length variants in recombinant inbred strains of mice placed the homologous mouse genes on distal Chr 10 near Ms15-8 and Mdm-1. The mouse Kcnc1 (KShIIIB, NGK2-KV4, KV3.1) gene mapped to Chr7 near Tam-1. These results are consistent with the hypothesis that the generation of the mammalian KCNC gene family included both duplication events to generate family members in tandem arrays (KCNC2, KCNC3) and dispersion of family members to unlinked chromosomal sites (KCNC1). The KNCN2 and KCNC3 genes define a new synteny group between humans and mice
— id: 17235, year: 1993, vol: 4, page: 711, stat: Journal Article,

Cloning and characterization of R-PTP-kappa, a new member of the receptor protein tyrosine phosphatase family with a proteolytically cleaved cellular adhesion molecule-like extracellular region
Jiang YP; Wang H; D'Eustachio P; Musacchio JM; Schlessinger J; Sap J
1993 May;13(5):2942-2951, Molecular & cellular biology
We describe a new member of the receptor protein tyrosine phosphatase family, R-PTP-kappa, cDNA cloning predicts that R-PTP-kappa is synthesized from a precursor protein of 1,457 amino acids. Its intracellular domain displays the classical tandemly repeated protein tyrosine phosphatase homology, separated from the transmembrane segment by an uncharacteristically large juxta-membrane region. The extracellular domain of the R-PTP-kappa precursor protein contains an immunoglobulin-like domain and four fibronectin type III-like repeats, preceded by a signal peptide and a region of about 150 amino acids with similarity to the Xenopus A5 antigen, a putative neuronal recognition molecule (S. Takagi, T. Hsrata, K. Agata, M. Mochii, G. Eguchi, and H. Fujisawa, Neuron 7:295-307, 1991). Antibodies directed against the intra- and extracellular domains reveal that the R-PTP-kappa precursor protein undergoes proteolytic processing, following which both cleavage products remain associated. By site-directed mutagenesis, the likely cleavage site was shown to be a consensus sequence for cleavage by the processing endopeptidase furin, located in the fourth fibronectin type III-like repeat. In situ hybridization analysis indicates that expression of R-PTP-kappa in the central nervous system is developmentally regulated, with highest expression seen in actively developing areas and, in the adult, in areas capable of developmental plasticity such as the hippocampal formation and cerebral cortex. The mouse R-PTP-kappa gene maps to chromosome 10, at approximately 21 centimorgans from the centromere
— id: 13177, year: 1993, vol: 13, page: 2942, stat: Journal Article,

Ran/TC4: a small nuclear GTP-binding protein that regulates DNA synthesis
Ren M; Drivas G; D'Eustachio P; Rush MG
1993 Jan;120(2):313-323, Journal of cell biology
Ran/TC4, first identified as a well-conserved gene distantly related to H-RAS, encodes a protein which has recently been shown in yeast and mammalian systems to interact with RCC1, a protein whose function is required for the normal coupling of the completion of DNA synthesis and the initiation of mitosis. Here, we present data indicating that the nuclear localization of Ran/TC4 requires the presence of RCC1. Transient expression of a Ran/TC4 protein with mutations expected to perturb GTP hydrolysis disrupts host cell DNA synthesis. These results suggest that Ran/TC4 and RCC1 are components of a GTPase switch that monitors the progress of DNA synthesis and couples the completion of DNA synthesis to the onset of mitosis
— id: 8315, year: 1993, vol: 120, page: 313, stat: Journal Article,

Chromosomal localization of uroplakin genes of cattle and mice
Ryan AM; Womack JE; Yu J; Lin JH; Wu XR; Sun TT; Clarke V; D'Eustachio P
1993 Nov;4(11):656-661, Mammalian genome
The asymmetric unit membrane (AUM) of the apical surface of mammalian urinary bladder epithelium contains several major integral membrane proteins, including uroplakins IA and IB (both 27 kDa), II (15 kDa), and III (47 kDa). These proteins are synthesized only in terminally differentiated bladder epithelial cells. They are encoded by separate genes and, except for uroplakins IA and IB, appear to be unrelated in their amino acid sequences. The genes encoding these uroplakins were mapped to chromosomes of cattle through their segregation in a panel of bovine x rodent somatic cell hybrids. Genes for uroplakins IA, IB, and II were mapped to bovine (BTA) Chromosomes (Chrs) 18 (UPK1A), 1 (UPK1B), and 15 (UPK2), respectively. Two bovine genomic DNA sequences reactive with a uroplakin III cDNA probe were identified and mapped to BTA 6 (UPK3A) and 5 (UPK3B). We have also mapped genes for uroplakins IA and II in mice, to the proximal regions of mouse Chr 7 (Upk1a) and 9 (Upk2), respectively, by analyzing the inheritance of restriction fragment length variants in recombinant inbred mouse strains. These assignments are consistent with linkage relationships known to be conserved between cattle and mice. The mouse genes for uroplakins IB and III were not mapped because the mouse genomic DNA fragments reactive with each probe were invariant among the inbred strains tested. Although the stoichiometry of AUM proteins is nearly constant, the fact that the uroplakin genes are unlinked indicates that their expression must be independently regulated. Our results also suggest likely positions for two human uroplakin genes and should facilitate further analysis of their possible involvement in disease
— id: 17236, year: 1993, vol: 4, page: 656, stat: Journal Article,

Immunodominance in the T-cell response to multiple non-H-2 histocompatibility antigens. V. Chromosomal mapping of the immunodominant cytotoxic T-cell target-1 (CTT-1)
Vagliani M; Melani C; Parmiani G; D'Eustachio P; Wettstein PJ; Colombo MP
1993 ;38(2):157-160, Immunogenetics
— id: 17237, year: 1993, vol: 38, page: 157, stat: Journal Article,

A novel receptor tyrosine phosphatase-sigma that is highly expressed in the nervous system
Yan H; Grossman A; Wang H; D'Eustachio P; Mossie K; Musacchio JM; Silvennoinen O; Schlessinger J
1993 Nov 25;268(33):24880-24886, Journal of biological chemistry
A novel transmembrane receptor protein tyrosine phosphatase-sigma (RPTP-sigma) was cloned from a rat brain stem cDNA library. The extracellular segment of one form of RPTP-sigma contains 824 amino acids and is composed of three immunoglobulin-like and five fibronectin type III (FNIII)-like repeats. The 627-amino acid cytoplasmic region of RPTP-sigma consists of two catalytic domains oriented in tandem. Northern blot analyses indicate that RPTP-sigma is highly expressed in the brain as two major transcripts of 5.7 and 6.9 kilobases (kb). The 5.7-kb transcript is expressed exclusively in the brain while the 6.9-kb species can be detected in the lung and heart, but at significantly lower levels. In situ hybridization studies confirm that RPTP-sigma is localized predominantly in the nervous system and can be detected in the rat as early as embryonic day 12. During embryonic development, RPTP-sigma is expressed extensively in the central and peripheral nervous systems, including the trigeminal and dorsal root ganglia as well as the retina. In adult rat brain, expression is restricted primarily to the olfactory tubercule, cerebellum, and hippocampus. Within the latter structure, RPTP-sigma is present in the pyramidal cell layer and granular layer of the dentate gyrus. Transfection of RPTP-sigma cDNA into human embryonic kidney 293 cells results in the synthesis of a protein with an apparent molecular mass of 200 kDa as detected by immunoprecipitation and immunoblot analyses using polyclonal antibodies against the FNIII-like repeats present in the extracellular domain of RPTP-sigma. The gene for RPTP-sigma has been mapped to distal chromosome 17 in the mouse
— id: 6558, year: 1993, vol: 268, page: 24880, stat: Journal Article,

Localization of growth arrest-specific genes on mouse chromosomes 1, 7, 8, 11, 13, and 16
Colombo MP; Martinotti A; Howard TA; Schneider C; D'Eustachio P; Seldin MF
1992 ;2(2):130-134, Mammalian genome
Growth arrest in NIH3T3 cells is associated with increased expression of a variety of mRNAs, several of which have been isolated as cDNA clones. Six of these growth arrest-specific (Gas) genes were mapped by following the inheritance of DNA restriction fragment length variants (RFLVs) associated with them in panels of recombinant inbred (RI) strains of mice and in the progeny of backcrosses both between laboratory mouse strains and between a laboratory strain and Mus spretus. The six genes are unlinked. Gas-1 maps to Chromosome (Chr) 13, Gas-2 to Chr 7, Gas-3 to Chr 11, Gas-4 to Chr 16, Gas-6 to Chr 8, and Gas-10 to Chr 1
— id: 17240, year: 1992, vol: 2, page: 130, stat: Journal Article,

Interpreting DNA fingerprints
D'Eustachio P
1992 Apr 9;356(6369):483-483, Nature
— id: 17238, year: 1992, vol: 356, page: 483, stat: Journal Article,

Mouse chromosome 12
D'Eustachio P
1992 ;3 Spec No:S182-S194, Mammalian genome
— id: 13767, year: 1992, vol: 3 Spec No, page: S182, stat: Journal Article,

A linkage map of mouse chromosome 1 using an interspecific cross segregating for the gld autoimmunity mutation
Watson ML; D'Eustachio P; Mock BA; Steinberg AD; Morse HC; Oakey RJ; Howard TA; Rochelle JM; Seldin MF
1992 ;2(3):158-171, Mammalian genome
An interspecific backcross was used to define a high resolution linkage map of mouse Chromosome (Chr) 1 and to analyze the segregation of the generalized lymphoproliferative disease (gld) mutation. Mice homozygous for gld have multiple features of autoimmune disease. Analysis of up to 428 progeny from the backcross [(C3H/HeJ-gld x Mus spretus)F1 x C3H/HeJ-gld] established a map that spans 77.6 cM and includes 56 markers distributed over 34 ordered genetic loci. The gld mutation was mapped to a less than 1 cM segment on distal mouse Chr 1 using 357 gld phenotype-positive backcross mice. A second backcross, between the laboratory strains C57BL/6J and SWR/J, was examined to compare recombination frequency between selected markers on mouse Chr 1. Significant differences in crossover frequency were demonstrated between the interspecific backcross and the inbred laboratory cross for the entire interval studied. Sex difference in meiotic crossover frequency was also significant in the laboratory mouse cross. Two linkage groups known to be conserved between segments of mouse Chr 1 and the long arm of human Chrs 1 and 2 where further defined and a new conserved linkage group was identified that includes markers of distal mouse Chr 1 and human Chr 1, bands q32 to q42
— id: 17239, year: 1992, vol: 2, page: 158, stat: Journal Article,

Establishment of left-right asymmetry in vertebrates: genetically distinct steps are involved
Brueckner M; McGrath J; D'Eustachio P; Horwich AL
1991 ;162(4):202-212, CIBA Foundation symposium
Vertebrates exhibit a characteristic pattern of asymmetrical positioning of the visceral organs along the left-right axis. A remarkable developmental step establishes this pattern--primitive organs migrate from symmetrical midline positions of origin into lateral positions. The first organ to pursue such movement is the cardiac tube, which forms a rightward 'D' loop; other organs follow concordantly. The signals and mechanisms directing such organ migration can be studied by analysis of heritable defects of humans and mice. In general, these defects behave as loss-of-function mutations that lead to random determination of visceral situs: for an affected embryo there is an equal chance of correct situs or situs inversus. Distinct phenotypes and patterns of inheritance of these defects suggest that at least three genes are involved in left-right determination, apparently members of a developmental pathway. These genes should be amenable to molecular analysis. We are studying a recessive allele of the mouse called inversus viscerum (iv). Using linkage analysis with cloned restriction fragment length polymorphism markers, we have genetically mapped the iv gene to the distal portion of mouse chromosome 12. We are now pursuing isolation of the gene using methods of positional cloning. Analysis of the iv gene product and of its site and timing of expression may offer clues to how left-right lateralization occurs
— id: 17242, year: 1991, vol: 162, page: 202, stat: Journal Article,

A linkage map of distal mouse chromosome 12
Cho M; Villani V; D'Eustachio P
1991 ;1(1):30-36, Mammalian genome
To refine the linkage map of distal mouse Chromosome 12, we have identified DNA restriction fragment variants associated with a creatine kinase gene (Ck-3), the Akt proto-oncogene, an Abelson proviral integration site (D12N1), and the immunoglobulin heavy chain VH3609 variable region family (Igh-V36). The patterns of inheritance of these markers in backcross progeny and recombinant inbred mouse strains allowed their localization with respect to previously mapped genes to yield the linkage map: Aat-15.8 cM-Ck-3-0.9 cM-(Crip, Akt, Igh-C)-0.3 cM-(D12N1, Igh-V). This map confirms genetically the localization of the Igh-V gene complex distal to Igh-C on the chromosome. It differs from previous maps in placing D12N1 distal to Igh-C, and in suggesting that the Igh-V gene complex spans less than one centiMorgan (cM). Other DNA sequence variants detected with the creatine kinase probe allowed definition of four additional genetic loci: Ck-1 near Lmyc-1 on Chromosome 4; Ck-2 between Upg-1 and Hprt-ps1 (D17Rp10) on distal Chromosome 17; Ck-4 near Mpmv-17 and Mls-3 on Chromosome 16; and Ck-5 near Hba on Chromosome 11
— id: 14215, year: 1991, vol: 1, page: 30, stat: Journal Article,

Mouse chromosome 12
D'Eustachio P
1991 ;1 Spec No:S192-S204, Mammalian genome
— id: 14213, year: 1991, vol: 1 Spec No, page: S192, stat: Journal Article,

The mouse polycystic kidney disease mutation (cpk) is located on proximal chromosome 12
Davisson MT; Guay-Woodford LM; Harris HW; D'Eustachio P
1991 Apr;9(4):778-781, Genomics
The mouse congenital polycystic kidney (cpk) mutation produces a condition that resembles human autosomal recessive polycystic kidney disease (ARPKD) in its pattern of inheritance, clinical progression, and histopathology. Inheritance of this mouse mutation in crosses segregating the Rb(12.14)8Rma translocation chromosome and various DNA markers of Chromosome 12 have localized cpk to a site near D12Nyu2, approximately 7 cM from the centromere of Chromosome 12. This result suggests that the homologous PKD2 gene should be localized to either human chromosome 2p23-p25 or chromosome 7q22-q31
— id: 17241, year: 1991, vol: 9, page: 778, stat: Journal Article,

Ras-like genes and gene families in the mouse
Drivas G; Massey R; Chang HY; Rush MG; D'Eustachio P
1991 ;1(2):112-117, Mammalian genome
Four human RAS-like cDNAs and a mouse genomic DNA fragment were used to define novel mouse Ras-like genes and gene families. Inheritance of DNA restriction fragment length variants associated with these genes in recombinant inbred and backcross mice allowed definition of 12 genetic loci, nine of which were mapped, to chromosomes (Chr) 2, 4, 7, 8, 9, and 17. Two possible clusters of Ras-like and/or G protein genes were identified, on Chrs 9 and 17
— id: 14229, year: 1991, vol: 1, page: 112, stat: Journal Article,

Evolutionary grouping of the RAS-protein family
Drivas GT; Palmieri S; D'Eustachio P; Rush MG
1991 May 15;176(3):1130-1135, Biochemical & biophysical research communications
Over 50 proteins related to the mammalian H-, K-, and N-RAS GTP binding and hydrolyzing proteins are known. These relatively low molecular weight proteins are usually grouped into four subfamilies, termed true RAS, RAS-like, RHO, and RAB/YPT, based on the presence of shared amino acid sequence motifs in addition to those involved in guanine nucleotide binding. Here, we apply parsimony analysis to the overall amino acid sequences of these proteins to infer possible phylogenetic relationships among them
— id: 14020, year: 1991, vol: 176, page: 1130, stat: Journal Article,

Identification and characterization of a human homolog of the Schizosaccharomyces pombe ras-like gene YPT-3
Drivas GT; Shih A; Coutavas EE; D'Eustachio P; Rush MG
1991 Jan;6(1):3-9, Oncogene
The Polymerase Chain Reaction was used to amplify ras and ras-like sequences from two human cDNA libraries. Members corresponding to each of the three major ras-subfamilies (ras, rho, and rab/YPT) were identified. The one homologous to rab/YPT, referred to here as YL8, appears to be the human homolog of the recently reported Schizosaccharomyces pombe YPT3 gene. The YL8 gene could encode a guanine nucleotide binding protein of 216 amino acids with about 70% amino acid sequence identity to S. pombe YPT3, and is transcriptionally active in a variety of human cell lines
— id: 14227, year: 1991, vol: 6, page: 3, stat: Journal Article,

Linkage of acid alpha-glucosidase (Gaa) and thymidine kinase (Tk-1) to esterase-3 (Es-3) on mouse chromosome 11
Martiniuk F; Hirschhorn R; D'Eustachio P
1991 ;1(4):267-269, Mammalian genome
Inheritance in recombinant inbred (RI) strains of restriction fragment length variants (RFLVs) detected by probes specific for Gaa and Tk-1 showed tight linkage of both to Es-3 on mouse Chromosome (Chr) 11. This result extends the region of homology between mouse Chr 11 and human chr 17q
— id: 14214, year: 1991, vol: 1, page: 267, stat: Journal Article,

Rat ribophorin II: molecular cloning and chromosomal localization of a highly conserved transmembrane glycoprotein of the rough endoplasmic reticulum
Pirozzi G; Zhou ZM; D'Eustachio P; Sabatini DD; Kreibich G
1991 May 15;176(3):1482-1486, Biochemical & biophysical research communications
We report here the complete nucleotide sequence of rat ribophorin II. The predicted amino acid sequence is highly homologous to the corresponding human protein and consists of 631 amino acid residues, including a 22 amino acid N-terminal cleavable signal sequence, and a single 23 amino acid putative transmembrane domain. Northern blot analysis reveals a single -2.4 kb message expressed in a number of rat cell lines and in adult liver. The gene was mapped to mouse chromosome 2, close to the Src proto-oncogene
— id: 14023, year: 1991, vol: 176, page: 1482, stat: Journal Article,

Structure and chromosome assignment of the murine p36 (calpactin I heavy chain) gene
Amiguet P; D'Eustachio P; Kristensen T; Wetsel RA; Saris CJ; Hunter T; Chaplin DD; Tack BF
1990 Feb 6;29(5):1226-1232, Biochemistry
p36 is a major substrate of both viral and growth factor receptor associated protein kinases. This protein has recently been named calpactin I heavy chain since it is the large subunit of a Ca2(+)-dependent phospholipid and actin binding heterotetramer. The primary structure of p36 has been determined from analysis of cloned cDNA. The protein contains 338 amino acids, has an approximate molecular weight of 39,000, and is comprised of several distinct domains, including four 75 amino acid repeats. From two overlapping cosmid clones isolated from different mouse genomic liver libraries, the complete intron/exon structure of the p36 gene was determined and the 5' and 3' noncoding regions of the gene were analyzed. The coding and 3' untranslated region of the p36 gene contains 12 exons which range in size from 48 to 322 base pairs (bp) with an average size of 107 bp. The repeat structures found at the protein level are not delineated by single exons, but the N-terminal p11-binding domain is encoded by a single exon. Structural mapping of the gene demonstrated that the lengths of the first two introns in the coding region are together approximately 6 kilobases (kb), while the other introns range in size from 600 to 3600 bp with an average size of 1650 bp. The p36 gene is at least 22 kb in length and has a coding sequence of approximately 1 kb, representing only 4.5% of the gene.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 17248, year: 1990, vol: 29, page: 1226, stat: Journal Article,

Structure and chromosomal location of the rat ribophorin I gene
Behal A; Prakash K; D'Eustachio P; Adesnik M; Sabatini DD; Kreibich G
1990 May 15;265(14):8252-8258, Journal of biological chemistry
Ribophorin I is a type I transmembrane glycoprotein characteristic of the rough portions of the endoplasmic reticulum where it is thought to play a role in the cotranslational insertion of nascent polypeptides. A rat ribophorin I cDNA was used to isolate four overlapping genomic clones from a rat EMBL3 genomic library. Restriction mapping, Southern blotting, and DNA sequencing showed that these clones, spanning approximately 21 kilobases of chromosomal DNA, include the entire ribophorin I gene, as well as 15 kilobases (kb) of upstream sequences. Southern blotting analysis of DNA from a panel of mouse-Chinese hamster cell hybrids demonstrated that the ribophorin I gene is located on mouse chromosome six. The ribophorin I gene contains 10 exons, seven of which encode the luminal domain of the polypeptide. Exon 8 encodes the trans-membrane domain and small portions of the flanking luminal and cytoplasmic domains. Exons 9 and 10 encode the remainder of the cytoplasmic domain, and the latter includes the 3'-untranslated portion of the mRNA. Six closely spaced transcription start sites located 3 to 24 base pairs upstream from the initiation codon were identified by primer extension analysis and S1 mapping. The sequence of a 1.3-kb region upstream of the cap sites was determined and found to contain three GC-rich potential Sp1-binding sites beginning at -14, -24, and -91 base pairs (bp), two octamer-like sequences at -233 and -1248 bp, and a CAAT-like box at -41 bp. The possible roles of these elements in regulating expression of the ribophorin gene in all cells and in differentiated cell types characterized by a well developed rough endoplasmic reticulum is discussed
— id: 17245, year: 1990, vol: 265, page: 8252, stat: Journal Article,

Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line
Drivas GT; Shih A; Coutavas E; Rush MG; D'Eustachio P
1990 Apr;10(4):1793-1798, Molecular & cellular biology
A mixed-oligonucleotide probe was used to identify four ras-like coding sequences in a human teratocarcinoma cDNA library. Two of these sequences resembled the rho genes, one was closely related to H-, K-, and N-ras, and one shared only the four sequence domains that define the ras gene superfamily. Homologs of the four genes were found in genomic DNA from a variety of mammals and from chicken. The genes were transcriptionally active in a range of human cell types
— id: 17246, year: 1990, vol: 10, page: 1793, stat: Journal Article,

Cloning and expression of a widely expressed receptor tyrosine phosphatase
Sap J; D'Eustachio P; Givol D; Schlessinger J
1990 Aug;87(16):6112-6116, Proceedings of the National Academy of Sciences of the United States of America
We describe the identification of a widely expressed receptor-type (transmembrane) protein tyrosine phosphatase (PTPase; EC 3.1.3.48). Screening of a mouse brain cDNA library under low-stringency conditions with a probe encompassing the intracellular (phosphatase) domain of the CD45 lymphocyte antigen yielded cDNA clones coding for a 794-amino acid transmembrane protein [hereafter referred to as receptor protein tyrosine phosphatase alpha (R-PTP-alpha)] with an intracellular domain displaying clear homology to the catalytic domains of CD45 and LAR (45% and 53%, respectively). The 142-amino acid extracellular domain (including signal peptide) of R-PTP-alpha is marked by a high serine/threonine content (32%) as well as eight potential N-glycosylation sites but displays no similarity to known proteins. Genetic mapping assigns the gene for R-PTP-alpha to mouse chromosome 2, closely linked to the Il-1a and Bmp-2a loci. The corresponding mRNA (3.0 kilobases) is expressed in most murine tissues and most abundantly expressed in brain and kidney. Antibodies against a synthetic peptide of R-PTP-alpha identified a 130-kDa protein in cells transfected with the R-PTP-alpha cDNA
— id: 17244, year: 1990, vol: 87, page: 6112, stat: Journal Article,

Identification of a new V kappa gene family that is highly expressed in hybridomas from an autoimmune mouse strain
Shefner R; Mayer R; Kaushik A; D'Eustachio P; Bona C; Diamond B
1990 Sep 1;145(5):1609-1614, Journal of immunology
We have identified a new murine V kappa family that contains five to seven members, one member of which encodes the L chain V region of an anti-dsDNA antibody produced by a BALB/c hybridoma, C8.5. The cloned C8.5 V kappa gene exhibits highest homology with a human V kappa gene that was cloned from a nonproductive rearrangement but has never been seen in an expressed repertoire. Because this family was first identified in an autoantibody, we studied its expression in an autoimmune mouse strain. This V kappa family is expressed in 20% of hybridomas from NZB mice
— id: 17243, year: 1990, vol: 145, page: 1609, stat: Journal Article,

Clustering of cytokine genes on mouse chromosome 11
Wilson SD; Billings PR; D'Eustachio P; Fournier RE; Geissler E; Lalley PA; Burd PR; Housman DE; Taylor BA; Dorf ME
1990 Apr 1;171(4):1301-1314, Journal of experimental medicine
The presence of positionally conserved amino acid residues suggests that the mouse proteins TCA3, P500, MIP1-alpha, MIP1-beta, and JE are members of a single gene family. These proteins are activation specific and can be expressed by both myeloid and lymphoid cells. MIP1-alpha/MIP1-beta and MCAF (the putative human homologue of JE) act as chemotactic and activating agents for neutrophils and macrophages, respectively. The functions of TCA3 and P500 are unknown. We have used interspecies somatic cell hybrids and recombinant inbred mouse strains to show that the genes encoding TCA3, MIP1-alpha, MIP1-beta, and JE (provisionally termed Tca3, Mip-1a, Mip-1b, and Sigje, respectively) map as a cluster on the distal portion of mouse chromosome 11 near the Hox-2 gene complex. DNA sequence analysis indicates that the P500 and TCA3 proteins are encoded by alternative splicing products of one genomic gene. Additionally, the genes encoding TCA3 and JE are found to be strikingly similar with respect to the positions of intron-exon boundaries. Together, these data support the model that the cytokines TCA3, P500, MIP1-alpha, MIP1-beta, and JE are encoded by a single cluster of related genes. The gene encoding IL-5 (Il-5), which acts as a T cell-replacing factor, a B cell growth factor, and an eosinophil differentiation factor, is also mapped to mouse chromosome 11.Il-5 maps approximately 25 cM proximal to the Tca-3 gene and appears tightly linked to a previously described gene cluster that includes Il-3, Il-4, and Csfgm. We discuss the potential relevance of the two cytokine gene clusters described here with particular attention to specific human hematologic malignancies associated with chromosomal aberrations at corresponding locations on human chromosomes 5 and 17
— id: 17247, year: 1990, vol: 171, page: 1301, stat: Journal Article,

Linkage mapping of a mouse gene, iv, that controls left-right asymmetry of the heart and viscera
Brueckner M; D'Eustachio P; Horwich AL
1989 Jul;86(13):5035-5038, Proceedings of the National Academy of Sciences of the United States of America
Inherited single gene defects have been identified in both humans and mice that lead to loss of developmental control over the left-right asymmetry of the heart and viscera. In mice the recessively inherited mutation iv leads to such apparent loss of control over situs: 50% of iv/iv mice exhibit situs inversus and 50% exhibit normal situs. The affected gene product has not been identified in these animals. To study the normal function of iv, we have taken an approach directed to the gene itself. As a first step, we have mapped iv genetically, by examining its segregation in backcrosses with respect to markers defined by restriction fragment length polymorphisms. The iv locus lies 3 centimorgans (cM) from the immunoglobulin heavy-chain constant-region gene complex (Igh-C) on chromosome 12. A multilocus map of the region suggests the gene order centromere-Aat (alpha 1-antitrypsin gene complex)-(11 cM)-iv-(3 cM)-Igh-C-(1 cM)-Igh-V (immunoglobulin heavy-chain variable-region gene complex)
— id: 17249, year: 1989, vol: 86, page: 5035, stat: Journal Article,

Chromosomal location of N-myc and L-myc genes in the mouse
Campbell GR; Zimmerman K; Blank RD; Alt FW; D'Eustachio P
1989 ;4(1):47-54, Oncogene research
The myc family of proto-oncogenes consists of at least three members, whose expression is tightly and co-ordinately regulated. The genes are nevertheless dispersed to three distinct chromosomal sites in humans. We have now used somatic cell genetics and the analysis of restriction fragment length polymorphisms (RFLPs) to identify and chromosomally map two mouse N-myc loci, to chromosomes 12 and 5, and two L-myc loci, provisionally to chromosomes 4 and 12. The second locus in each pair may be a pseudogene
— id: 10794, year: 1989, vol: 4, page: 47, stat: Journal Article,

Comparison of linkage maps of mouse chromosome 12 derived from laboratory strain intraspecific and Mus spretus interspecific backcrosses
Seldin MF; Howard TA; D'Eustachio P
1989 Jul;5(1):24-28, Genomics
Progeny from an interspecific backcross between laboratory mice and Mus spretus were typed for inheritance of eight genetic markers on chromosome 12. Marker order determined by segregation analyses of 115 meiotic events was in good agreement with that determined previously using intraspecific laboratory strain backcrosses. Two additional markers, D12Nyu5 and Lamb-1, previously not ordered, were located in the middle of the interval between D12Nyu12 and D12Nyu1. Marker spacing was reduced in the interspecific cross relative to that observed in intraspecific crosses. Furthermore, the interspecific cross was characterized by marked deviation from 1:1 segregation in the recombinant chromosomes and very strong positive interference. These data suggest that comparisons of different mouse crosses may facilitate the understanding of underlying mechanisms that govern recombination events in complex genomes
— id: 17250, year: 1989, vol: 5, page: 24, stat: Journal Article,

Linkage genetics of mouse ornithine decarboxylase (Odc)
Villani V; Coffino P; D'Eustachio P
1989 Oct;5(3):636-638, Genomics
Ornithine decarboxylase (ODC) is synthesized as a single polypeptide in the mouse, but DNA sequences reactive with ODC cDNA probes have been mapped to multiple mouse chromosomes. A DNA fragment from the untranscribed 5' flank of a transcriptionally active ODC gene has been used as a probe to define a restriction fragment length polymorphism associated with the gene. The pattern of inheritance of this polymorphism in recombinant inbred strains of mice and in progeny of a conventional backcross localized it to proximal chromosome 12. This result confirms previous experiments with somatic cell hybrids that mapped the gene to chromosome 12 and further defines the linkage group conserved between proximal chromosome 12 and human chromosome 2p. The other ODC homologs are tentatively identified as cDNA-like pseudogenes
— id: 10480, year: 1989, vol: 5, page: 636, stat: Journal Article,

Chromosomal locations of genes encoding 2',3' cyclic nucleotide 3'-phosphodiesterase and glial fibrillary acidic protein in the mouse
Bernier L; Colman DR; D'Eustachio P
1988 Aug;20(4):497-504, Journal of neuroscience research
Cyclic nucleotide phosphodiesterase (CNP) and glial fibrillary acidic protein (GFAP) are useful markers of myelin and astroglia, respectively. Two proteins with CNP activity are known to exist in brain and lymphoid tissues. They appear to be the products of several distinct but related messenger ribonucleic acid (mRNA) species. GFAP is a single protein encoded by a single mRNA. We have localized the GFAP gene to distal chromosome 11 in the mouse. There are two genetic loci identified by CNP probes, one is closely linked to the GFAP gene, and the other maps to chromosome 3
— id: 17251, year: 1988, vol: 20, page: 497, stat: Journal Article,

A linkage map of mouse chromosome 12: localization of Igh and effects of sex and interference on recombination
Blank RD; Campbell GR; Calabro A; D'Eustachio P
1988 Dec;120(4):1073-1083, Genetics
Inheritance of restriction fragment length polymorphisms associated with four anonymous DNA markers (D12Nyu1, 2, 3 and 4), the Fos proto-oncogene, the Mtv-9 viral integration site, and the alpha 1-antitrypsin (Aat-1) and immunoglobulin heavy chain (Igh) gene families in the mouse has been followed in a backcross experiment. A Bayesian multilocus map-building strategy yielded the map: centromere-D12Nyu2-10 cM-D12Nyu1-2 cM-D12Nyu3-15 cM-Fos-1 cM-D12Nyu4-2 cM-Mtv-9-8 cM-Aat-1-17 cM-Igh-C. A map constructed from male meiotic data was substantially shorter than one constructed from female meiotic data. Significant interference was observed for the linkage group. Two groups of markers studied in recombinant inbred strains of mice could be interpolated into the map: Es-25, D12Nyu10, D12Nyu7 and Apob form a cluster proximal to D12Nyu2, and Ly-18, Ah, and D12Nyu5 form a cluster between D12Nyu2 and D12Nyu1. These data establish an unambiguously ordered linkage group including Igh and Aat-1 that spans most of chromosome 12
— id: 10872, year: 1988, vol: 120, page: 1073, stat: Journal Article,

Bayesian multilocus linkage mapping
Blank RD; Campbell GR; Pollak M; D'Eustachio P
1988 ;137(2):25-32, Current topics in microbiology & immunology
— id: 17252, year: 1988, vol: 137, page: 25, stat: Journal Article,

The IL-4 gene maps to chromosome 11, near the gene encoding IL-3
D'Eustachio P; Brown M; Watson C; Paul WE
1988 Nov 1;141(9):3067-3071, Journal of immunology
IL-4/B cell stimulatory factor 1 (IL-4) is a potent mediator of the growth and differentiation of cells of most hemopoietic lineages. IL-4 is one of a number of lymphokines produced by T cells after activation with Ag or mitogen. In order to map the chromosomal location of the IL-4 gene, Chinese hamster-mouse somatic cell hybrids were used in Southern blot analyses with an IL-4 cDNA probe. These results suggested that the IL-4 gene was located on chromosome 11. In contrast, the gene encoding IL-2 was localized to either chromosome 1 or 3. The identification of a strain-specific Bgl II restriction enzyme polymorphism in the IL-4 gene was used to map the IL-4 gene to a position on mouse chromosome 11 within 1 centimorgan of the gene encoding IL-3
— id: 10921, year: 1988, vol: 141, page: 3067, stat: Journal Article,

Chromosomal location of the mouse gene that encodes the myelin-associated glycoproteins
D'Eustachio P; Colman DR; Salzer JL
1988 Feb;50(2):589-593, Journal of neurochemistry
The two myelin-associated glycoprotein (MAG) species, designated large MAG (L-MAG) and small MAG (S-MAG), are believed to be generated by differential splicing from a single RNA transcript. We have now defined the genetic locus encoding the two MAG proteins in the mouse. Analysis of a panel of interspecies somatic cell hybrids indicated that all MAG coding sequences reside on chromosome 7. Following the inheritance of a restriction fragment length polymorphism associated with MAG coding sequences allowed the locus to be positioned 0.5 centimorgans from the locus Abpa (androgen binding protein alpha) on proximal chromosome 7. These data strongly support the hypothesis that a single gene encodes the two MAG proteins, and we propose the name Mag for this locus. This localization places Mag in close proximity to the neurological mutant locus qv (quivering) and raises the possibility of a functional relationship or identity between Mag and qv. However, an analysis of the MAG gene, its RNA transcripts, and its protein products revealed no abnormalities in homozygous qv mutant mice, suggesting that this chromosomal linkage is not etiologically significant
— id: 11203, year: 1988, vol: 50, page: 589, stat: Journal Article,

cDNA cloning of esterase 1, the major esterase activity in mouse plasma
Genetta TL; D'Eustachio P; Kadner SS; Finlay TH
1988 Mar 30;151(3):1364-1370, Biochemical & biophysical research communications
We report here the cloning of a partial cDNA for Esterase 1, the major esterase activity in mouse plasma. A 470 base pair insert was isolated from a lambda gt11 cDNA library constructed from mouse liver poly A+ RNA, and identified by hybrid selected translation. We show that the sexual dimorphism displayed in the plasma levels of this protein is caused by a difference at the level of transcription. In addition, RFLP data using mouse recombinant inbred strains mapped this clone at the Es-1 locus on mouse chromosome 8
— id: 11152, year: 1988, vol: 151, page: 1364, stat: Journal Article,

Mouse N-ras genes: organization of the functional locus and of a truncated cDNA-like pseudogene
Chang HY; Guerrero I; Lake R; Pellicer A; D'Eustachio P
1987 Jul;1(2):129-136, Oncogene research
The N-ras gene was first identified in both humans and mice as a mutationally activated oncogene found in tumors. The nucleotide sequence and intron/exon structure of the coding region of the mouse gene have been determined previously. We have now determined the sequence and intron/exon structure of the 5' and 3' untranslated regions of mouse N-ras. Like its human homolog, the 3' untranslated region of the gene is encoded by two exons, and the 5' region is encoded by one. In addition, we have isolated and sequenced a second mouse gene homologous to N-ras. This locus, which we have named N-ras-2ps, resides at a chromosomal site distinct from N-ras and appears to be a truncated cDNA-like pseudogene
— id: 11391, year: 1987, vol: 1, page: 129, stat: Journal Article,

Cellular DNA rearrangements and early developmental arrest caused by DNA insertion in transgenic mouse embryos
Covarrubias L; Nishida Y; Terao M; D'Eustachio P; Mintz B
1987 Jun;7(6):2243-2247, Molecular & cellular biology
Insertional mutagenesis was investigated in a transgenic mouse strain (HUGH/4) derived from a fertilized egg injected with plasmid DNA containing the human growth hormone gene. Lethality occurred in homozygous embryos and was traced to the egg cylinder stage on days 4 to 5 of gestation, shortly after implantation. The mutation is on chromosome 12 and is distinct in location and integration pattern from another mutation also leading to lethality of homozygotes in the egg cylinder stage. Based on this and other evidence, relatively many genes may be recruited to activity near the time of implantation and may therefore present a large target of vulnerability to mutagenesis. The single insert in HUGH/4, consisting of approximately three tandem copies of plasmid sequences, is flanked by mouse cellular sequences that have undergone rearrangements, including a probable deletion. The data suggest the hypothesis that DNA rearrangements, which appear to be commonplace in transgenic mice, may arise because the initial insertional complex is unstable; stepwise changes may then be generated until a more stable conformation is achieved
— id: 17255, year: 1987, vol: 7, page: 2243, stat: Journal Article,

Interleukin-1 alpha and beta genes: linkage on chromosome 2 in the mouse
D'Eustachio P; Jadidi S; Fuhlbrigge RC; Gray PW; Chaplin DD
1987 ;26(6):339-343, Immunogenetics
Two interleukin-1 polypeptides, alpha and beta, are known, and cDNAs corresponding to each have been described. Genomic cloning and Southern blotting experiments suggest that in the mouse each is encoded by a gene present in one copy per haploid genome. Analysis of a panel of somatic cell hybrids carrying various mouse chromosomes on a constant Chinese hamster background indicates that both genes map to mouse chromosome 2. Further, analysis of the inheritance of DNA restriction fragment length polymorphisms associated with each gene in recombinant inbred strains of mice shows the two loci to be tightly linked to one another, and to lie approximately 4.7 centimorgans distal to B2m (beta-2 microglobulin). We have named the locus encoding IL-1 alpha Il-1 alpha and the locus encoding IL-1 beta Il-1b
— id: 11428, year: 1987, vol: 26, page: 339, stat: Journal Article,

The gene encoding the mouse T cell differentiation antigen L3T4 is located on chromosome 6
Field EH; Tourvieille B; D'Eustachio P; Parnes JR
1987 Mar 15;138(6):1968-1970, Journal of immunology
We have used Southern blot analysis of DNA from somatic cell hybrids to map the chromosomal location of the mouse L3T4 T cell differentiation antigen gene to chromosome 6. This finding is of interest because both L3T4 and the alternative T cell differentiation antigen Lyt-2 are homologous to kappa-immunoglobulin light chain-variable regions, and the genes encoding kappa and Lyt-2 are also located on mouse chromosome 6
— id: 17257, year: 1987, vol: 138, page: 1968, stat: Journal Article,

The superfamily of C3b/C4b-binding proteins
Kristensen T; D'Eustachio P; Ogata RT; Chung LP; Reid KB; Tack BF
1987 May 15;46(7):2463-2469, Federation Proceedings (Federation of American Societies for Experimental Biology)
The determination of primary structures by amino acid and nucleotide sequencing for the C3b-and/or C4b-binding proteins H, C4BP, CR1, B, and C2 has revealed the presence of a common structural element. This element is approximately 60 amino acids long and is repeated in a tandem fashion, commencing at the amino-terminal end of each molecule. Two other complement components, C1r and C1s, have two of these repeating units in the carboxy-terminal region of their noncatalytic A chains. Three noncomplement proteins, beta 2-glycoprotein I (beta 2I), the interleukin 2 receptor (IL 2 receptor), and the b chain of factor XIII, have 4, 2 and 10 of these repeating units, respectively. These proteins obviously belong to the above family, although there is no evidence that they interact with C3b and/or C4b. Human haptoglobin and rat leukocyte common antigen also contain two and three repeating units, respectively, which have more limited homology with the repetitive regions in this family. All available data indicate that multiple gene duplications and exon shuffling have been important features in the divergence of this family of proteins with the 60-amino-acid repeat
— id: 17256, year: 1987, vol: 46, page: 2463, stat: Journal Article,

Structure and evolutionary origin of the gene encoding mouse NF-M, the middle-molecular-mass neurofilament protein
Levy E; Liem RK; D'Eustachio P; Cowan NJ
1987 Jul 1;166(1):71-77, European journal of biochemistry
We describe the complete sequence of the gene encoding mouse NF-M, the middle-molecular-mass neurofilament protein. The coding sequence is interrupted by two intervening sequences which align perfectly with the first two intervening sequences in the gene encoding NF-L (the low-molecular-mass neurofilament protein); there is no intron in the gene encoding NF-M corresponding to the third intron in NF-L. Therefore, both the number of introns and their arrangement in the genes coding NF-L and NF-M contrast sharply with the number and arrangement of introns in the genes of known sequence, encoding other members of the intermediate filament multigene family (desmin, vimentin, glial fibrillary acidic protein and the acidic and basic keratins); with the exception of a single truncated keratin gene that lacks an encoded tailpiece, these genes all contain eight introns, of which at least six are placed at homologous locations. Assuming the existence of a primordial intermediate filament gene containing most (if not all) the introns found in contemporary non-neurofilament intermediate filament genes, it seems likely that an RNA-mediated transposition event was involved in the generation of an ancestral gene encoding the NF polypeptides. A combination of insertional transposition and gene-duplication events could then explain the anomalous number and placement of introns within these genes. Consistent with this notion, we show that the genes encoding NF-M and NF-L are linked
— id: 17141, year: 1987, vol: 166, page: 71, stat: Journal Article,

Assignment of the Ly-6--Ril-1--Sis--H-30--Pol-5/Xmmv-72--Ins-3--Krt-1--Int-1 --Gdc-1 region to mouse chromosome 15
Meruelo D; Rossomando A; Scandalis S; D'Eustachio P; Fournier RE; Roop DR; Saxe D; Blatt C; Nesbitt MN
1987 ;25(6):361-372, Immunogenetics
Previous work has demonstrated linkage between Ly-6, H-30, and a locus, Ril-1, that affects susceptibility to radiation-induced leukemia. Results or preliminary linkage analyses suggested further that the cluster might be linked to Ly-11 on the proximal portion of mouse chromosome 2. Using molecular probes to examine somatic cell lines and recombinant inbred and congenic strains of mice, we have re-evaluated these linkage relationships. A cloned genomic DNA fragment derived from a retroviral site has been used to define a novel locus, Pol-5, that is tightly linked to both H-30 and Ril-1 as shown by analysis of the B6.C-H-30c congenic mouse strain. Following the segregation of the Pol-5 mouse-specific DNA fragment in a series of somatic cell hybrids carrying various combinations of mouse chromosomes on a rat or Chinese hamster background mapped Pol-5 to mouse chromosome 15. During the course of these studies, restriction fragment length polymorphisms were defined associated with several loci, including Pol-5, Ly-6, Sis, Ins-3, Krt-1, Int-1, and Gdc-1. Three of these loci, Sis, Int-1, and Gdc-1, have been previously mapped to chromosome 15 by others using somatic cell hybrids or isoenzyme analyses. Following the inheritance of these eight loci in recombinant inbred strains of mice allowed the definition of a linkage group on the chromosome with the order Ly-6--Ril-1--Sis--H-30--Pol-5--Ins-3--Krt-1--Int-1--Gdc-1. Analyses of alleles inherited as passengers in B6.C-H-30c, C3H.B-Ly-6b, and C57BL/6By-Eh/+ congenic mouse strains and in situ hybridization experiments support the above gene order and indicate further that the cluster is located on distal chromosome 15, with Ly-6 and Sis near Eh
— id: 15248, year: 1987, vol: 25, page: 361, stat: Journal Article,

Murine Hox-1.7 homeo-box gene: cloning, chromosomal location, and expression
Rubin MR; King W; Toth LE; Sawczuk IS; Levine MS; D'Eustachio P; Nguyen-Huu MC
1987 Oct;7(10):3836-3841, Molecular & cellular biology
A new murine homeo-box, called Hox-1.7, has been identified in a rare cDNA from F9 teratocarcinoma stem cells. The Hox-1.7 homeo-box is 68 and 72% homologous to the Drosophila antennapedia (Antp) and iab-7 homeo-boxes, respectively. A major 2.5-kilobase transcript and several minor transcripts were detected by Northern blot (RNA blot) analysis in adult tissues as well as in midgestational embryos. The posterior spinal cord was found to be a major site of Hox-1.7 expression in 12.5-day-old embryos. Somatic cell hybrids were used to map the Hox-1.7 gene to mouse chromosome 6. Restriction fragment length polymorphisms associated with either the Hox-1.7 gene or the previously known Hox-1 complex were identified. Their distribution patterns in recombinant inbred mouse strains were used to determine the linkage between the two loci as well as to other loci on chromosome 6. This maps Hox-1 and Hox-1.7 close to two mouse loci that affect morphogenesis, postaxial hemimelia (px) and hypodactyly (Hd)
— id: 17253, year: 1987, vol: 7, page: 3836, stat: Journal Article,

cDNA sequence and tissue distribution of the mRNA for bovine and murine p11, the S100-related light chain of the protein-tyrosine kinase substrate p36 (calpactin I)
Saris CJ; Kristensen T; D'Eustachio P; Hicks LJ; Noonan DJ; Hunter T; Tack BF
1987 Aug 5;262(22):10663-10671, Journal of biological chemistry
We have isolated and sequenced cDNA clones of bovine and murine p11 mRNAs. The nonpolyadenylated mRNAs are predicted to be 614 and 600 nucleotides, respectively. The p11 mRNAs both contain a 291 nucleotide open reading frame, preceded by a 5'-untranslated region of 73 nucleotides in bovine p11 mRNA and of 68 nucleotides in murine p11 mRNA. The deduced bovine p11 amino acid sequence is identical to the previously published partial bovine and complete porcine p11 protein sequence except for an additional COOH-terminal lysine residue. The bovine and murine p11 proteins are 92% homologous, whereas at the nucleotide level the conservation is 89% in the coding region and 75% in the 3'-untranslated region. Southern analysis of murine genomic DNA detected a single p11 gene, less than 10 kilobase pairs in size, containing as many as three introns. The p11 gene has been assigned to mouse chromosome 3 by analysis of interspecific hybrid cell panels and recombinant inbred mouse strains. The p11 gene is closely linked to the Xmmv-65 endogenous leukemia virus env gene and the guanylate binding protein-1 gene. Northern analyses of RNAs from mouse tissues and cell lines indicated that p11 mRNA levels vary widely. They are very low in liver, heart, and testes, moderate in brain, spleen, and thymus, and high in kidney, intestine, and lung. Analysis of the same RNA samples for p36 mRNA levels showed that expression of p11 and p36 mRNAs is not always coordinated. Brain and the mouse embryonal carcinoma cell line F9 contain moderate to high levels of p11 mRNA with very low levels of p36 mRNA. Sequence homology between p11 and the S100 proteins, and the serum-induced 2A9 gene product, as well as possible functions of p11 are discussed
— id: 17254, year: 1987, vol: 262, page: 10663, stat: Journal Article,

Three functional ribosomal protein genes are unlinked in mouse genome
Wiedemann LM; D'Eustachio P; Kelley DE; Perry RP
1987 Jan;13(1):77-80, Somatic cell & molecular genetics
The mouse chromosomes bearing three functional ribosomal protein (rp) genes were identified by Southern blot analysis of DNA from a panel of mouse-hamster hybrid cell lines. Unique sequence intron probes were used to distinguish the functional rp genes from their multiple processed pseudogene counterparts. The genes specifying ribosomal proteins S16, L30, and L32 were found to be on chromosomes 7, 15, and 6, respectively. Since these functional rp genes are widely dispersed in the mouse genome, coordinate regulation of their transcriptional activity cannot be accomplished by a structural alteration of a single chromosomal region. Rather, it would have to involve interactions with sequences or structural motifs that are common to all three genes
— id: 17258, year: 1987, vol: 13, page: 77, stat: Journal Article,

Possible derivation of the laboratory mouse genome from multiple wild Mus species
Blank RD; Campbell GR; D'Eustachio P
1986 Dec;114(4):1257-1269, Genetics
Laboratory strains of mice are thought to be derived from wild populations of Mus domesticus. Many instances of non-domesticus genetic information fixed in these strains have been described, however, and the amount of strain-to-strain genetic variation exceeds that found in wild domesticus populations. In order to estimate the extent of the non-domesticus contribution to laboratory mouse genomes, and to determine whether it could account for observed variation, we have used computer simulations to investigate the properties of genetically marked chromosomal segments and the distribution of residual allogenicity at various times during inbreeding. A locus or chromosomal segment is allogenic if it is unfixed within a lineage at a given time. The odds of fixation of a foreign chromosome segment are predicted to be an exponentially decreasing function of its length. The median segment length is predicted to be 17 centimorgans. Available data for markers of chromosomes 1, 9 and 12 in recombinant inbred strain sets conform to these predictions. Together, the results suggest that introgression of non-domesticus chromosomes and segregation of residual allogenicity are sufficient to account for the genetic diversity observed among inbred mouse strains and substrains
— id: 17260, year: 1986, vol: 114, page: 1257, stat: Journal Article,

Chromosomal location of the genes encoding complement components C5 and factor H in the mouse
D'Eustachio P; Kristensen T; Wetsel RA; Riblet R; Taylor BA; Tack BF
1986 Dec 15;137(12):3990-3995, Journal of immunology
Complementary DNA probes corresponding to the factor H and C5 polypeptides have been used to determine the chromosomal localizations of these two complement components. Both probes revealed complex and polymorphic arrays of DNA fragments in Southern blot analysis of mouse genomic DNA. Following the distribution of these bands in panels of somatic cell hybrids carrying various combinations of mouse chromosomes on a constant rat or Chinese hamster background allowed the localization of the C5-associated fragments to proximal chromosome 2 and the localization of the factor H-associated fragments to chromosome 1 or chromosome 3. Following the inheritance of DNA restriction fragment-length polymorphisms revealed by the probes in recombinant inbred mouse strains allowed the factor H-associated fragments to be mapped to Sas-1 on chromosome 1, and the C5-associated fragments to be mapped to Hc. Analysis of three-point crosses, in turn, placed the latter locus 19 cM distal to Sd on chromosome 2. We have designated the two loci Cfh and C5, respectively. This genetic analysis raises the possibility that C5 and factor H are both encoded by complex loci composed of distinct structural and regulatory genes
— id: 17259, year: 1986, vol: 137, page: 3990, stat: Journal Article,

A mouse homeo box gene is expressed in spermatocytes and embryos
Rubin MR; Toth LE; Patel MD; D'Eustachio P; Nguyen-Huu MC
1986 Aug 8;233(4764):663-667, Science
The MH-3 gene, which contains a homeo box that is expressed specifically in the adult testis, was identified and mapped to mouse chromosome 6. By means of in situ hybridization with adult testis sections and Northern blot hybridization with testis RNA from prepuberal mice and from Sl/Sld mutant mice, it was demonstrated that this gene is expressed in male germ cells during late meiosis. In the embryo, MH-3 transcripts were present at day 11.5 post coitum, a stage in mouse development when gonadal differentiation has not yet occurred. The MH-3 gene may have functions in spermatogenesis and embryogenesis
— id: 17261, year: 1986, vol: 233, page: 663, stat: Journal Article,

Isolation of a cDNA clone corresponding to an X-linked gene family (XLR) closely linked to the murine immunodeficiency disorder xid
Cohen DI; Hedrick SM; Nielsen EA; D'Eustachio P; Ruddle F; Steinberg AD; Paul WE; Davis MM
1985 Mar 28-Apr 3;314(6009):369-372, Nature
The striking number of human and murine immunodeficiency disorders which map to the X chromosome suggests that genes localized on this chromosome must have important roles in lymphocyte development. At least seven distinct disorders in the human and two in the mouse disrupt lymphocyte maturation, particularly that of B cells, at characteristic stages. As functional genes mapping to the X chromosome in one mammal are found on the X chromosome in all other mammals, the same genes regulating lymphocyte development are expected to be found on the X chromosome in mouse and man. Investigations into the possible mechanisms of these X-linked disorders have been hampered by the lack of molecular probes for the genes or gene products affected; because of this, and the possibility of correlating one or more of the several hundred B- or T-cell-specific genes with a specific mutation, we surveyed 15 different B- and T-cell-specific cDNA clones for localization to the X chromosome. We report here the characterization of one of these murine cDNA clones, which hybridizes with a large, X-linked gene family, designated XLR (X-linked, lymphocyte-regulated). We show that the XLR gene family is closely linked to the X-linked immunodeficiency described in the CBA/N mouse strain (xid), by restriction fragment length polymorphism (RFLP) analysis of DNA from mice congeneic for xid. This finding, together with data on the expression of the XLR locus in B cells, indicates that this gene family either includes the locus defined by the xid mutation or is adjacent to it in a gene complex which may be important in lymphocyte differentiation
— id: 17265, year: 1985, vol: 314, page: 369, stat: Journal Article,

Chromosomal location of the gene encoding the neural cell adhesion molecule (N-CAM) in the mouse
D'Eustachio P; Owens GC; Edelman GM; Cunningham BA
1985 Nov;82(22):7631-7635, Proceedings of the National Academy of Sciences of the United States of America
The gene encoding the neural cell adhesion molecule, N-CAM, has been localized on mouse chromosome 9. A BALB/cJ mouse genomic library prepared in lambda bacteriophage EMBL4 was screened by using a cDNA probe, pEC204, that corresponds to the coding region of the chicken N-CAM gene. Four weakly reactive and one strongly reactive recombinant phage were isolated. A region of the latter that was strongly homologous to pEC204 was subcloned to yield a new probe, pEC501. RNA transfer blots and nucleotide sequencing indicated that pEC501 encoded part of the mouse N-CAM gene. This probe defined a unique genetic locus, Ncam, associated with a restriction fragment length polymorphism that allowed the definition of two alleles. The locus could be provisionally assigned either to chromosome 9 or to chromosome 10 by correlating the presence or absence of mouse-specific DNA fragments reactive with the probe in a panel of somatic hybrid cell lines with the presence or absence of the various mouse chromosomes. Analysis of the inheritance of the Ncam-associated DNA polymorphism in recombinant inbred strains of mice revealed close linkage between Ncam and the Lap-1, Sep-1, and Thy-1 loci on chromosome 9. This result suggests an additional linkage between Ncam and the locus for the cerebellar mutation staggerer (sg). The Ncam locus provides an important reference point for mapping the genes for additional cell adhesion molecules as well as genes for other molecules involved in neural development and function
— id: 17264, year: 1985, vol: 82, page: 7631, stat: Journal Article,

Carcinogen specificity in the activation of transforming genes by direct-acting alkylating agents
Garte SJ; Hood AT; Hochwalt AE; D'Eustachio P; Snyder CA; Segal A; Albert RE
1985 Dec;6(12):1709-1712, Carcinogenesis
DNAs from rat nasal and mouse skin carcinomas and fibrosarcomas induced by the alkylating agents methylmethane sulfonate (MMS), beta-propiolactone (BPL), and dimethylcarbamyl chloride (DMCC) were tested for their ability to transform NIH3T3 cells by DNA transfection. Each of eight MMS-induced rat nasal carcinomas and two of five BPL-induced mouse skin tumors were positive in the transfection assay while all of four fibrosarcomas and six carcinomas induced by DMCC were negative. Anchorage independent growth, tumorigenicity in nude mice, and secondary transfection confirmed the transformed phenotype of the positive transfectants. The transfectants from MMS-induced tumor DNAs did not contain restriction fragments homologous to rat H-, K- or N-ras oncogenes although exogenous (rat) tumor-derived DNA sequences were detected in transfectant genomes by Southern analysis. In contrast a BPL-induced mouse skin tumor showed evidence of containing activated H-ras. These results suggest specificity among causal chemical carcinogens for activation of transforming genes in experimental tumors
— id: 17262, year: 1985, vol: 6, page: 1709, stat: Journal Article,

An inherited limb deformity created by insertional mutagenesis in a transgenic mouse
Woychik RP; Stewart TA; Davis LG; D'Eustachio P; Leder P
1985 Nov 7-13;318(6041):36-40, Nature
We have created an insertional mutation that leads to a severe defect in the pattern of limb formation in the developing mouse. The novel recessive mutation is phenotypically identical and non-complementary to two previously encountered limb deformity mutations, and is closely linked to a dominant mutation that gives rise to a related limb dysmorphism. The inserted element thus provides a molecular genetic link with the control of pattern formation in the mammalian embryo
— id: 17263, year: 1985, vol: 318, page: 36, stat: Journal Article,

A genetic map of mouse chromosome 12 composed of polymorphic DNA fragments
D'Eustachio P
1984 Sep 1;160(3):827-838, Journal of experimental medicine
Mouse chromosome 12 encodes the heavy chains of immunoglobulins (Igh), a family of T cell surface molecules, and a tumor antigen that may be homologous to immunoglobulins. To refine and extend the genetic map of this chromosome, a procedure has been developed to isolate chromosome 12-specific DNA fragments from a somatic cell hybrid carrying the chromosome on a Chinese hamster background. Five fragments have been isolated and characterized in detail. All are polymorphic, defining loci D12-1, 2, 3, 4, and 5. Using recombinant inbred mouse strains, a tentative linkage map of chromosome 12 has been worked out that incorporates these markers, the c-fos oncogene, Igh, and Pre-1/alpha 1 antitrypsin. This strategy should be applicable to any mouse chromosome or chromosomal region that can be isolated in a somatic cell hybrid
— id: 17268, year: 1984, vol: 160, page: 827, stat: Journal Article,

The alpha-globin pseudogene on mouse chromosome 17 is closely linked to H-2
D'Eustachio P; Fein B; Michaelson J; Taylor BA
1984 Mar 1;159(3):958-963, Journal of experimental medicine
DNA sequences homologous to adult alpha-globin genes are dispersed in the mouse. Two functional genes are tightly linked on chromosome 11. Pseudogenes have been assigned to chromosomes 15 and 17 by analysis of interspecies somatic cell hybrids. We have now further characterized the second of these pseudogenes, Hba-a4. The gene is highly polymorphic, with three forms occurring in a panel of 15 inbred strains and a fourth occurring in an inbred strain derived from M. m. molossinus. Analysis of Hba-a4 alleles in CXB, BXH, and AKXL recombinant inbred strains placed Hba-a4 6.60 +/- 3.14 cM centromeric to H-2. Analysis of congenic mouse strains confirmed the linkage and the gene order. Hba-a4 is the first mammalian dispersed pseudogene to be localized in a linkage map, and should provide a useful marker for the region of chromosome 17 proximal to H-2
— id: 17269, year: 1984, vol: 159, page: 958, stat: Journal Article,

Isolation, characterization, and chromosome assignment of mouse N-ras gene from carcinogen-induced thymic lymphoma
Guerrero I; Villasante A; D'Eustachio P; Pellicer A
1984 Sep 7;225(4666):1041-1043, Science
Treatment of mice with the carcinogen N-methylnitrosourea results in the development of thymic lymphomas with frequent involvement of the N-ras oncogene. The activated mouse N-ras gene was isolated from one of these lymphomas and, by transformation in concert with restriction digestion, a map of the gene was prepared and its approximate boundaries were determined. By means of somatic cell hybrids the normal N-ras gene was found to be unlinked to other members of the ras gene family
— id: 17266, year: 1984, vol: 225, page: 1041, stat: Journal Article,

Confirmation of the regional localization of the genes for human acid alpha-glucosidase (GAA) and adenosine deaminase (ADA) by somatic cell hybridization
Honig J; Martiniuk F; D'Eustachio P; Zamfirescu C; Desnick R; Hirschhorn K; Hirschhorn LR; Hirschhorn R
1984 Jan;48(Pt 1):49-56, Annals of human genetics
We have confirmed the localization of human acid alpha-glucosidase (GAA) to 17q21----q25 and of adenosine deaminase (ADA) to 20q13----20qter by examination of hybrid clones derived from a fusion between a human cell line carrying a 17/20 balanced translocation (17pter----17q25::20q13----20qter;20pter-- --20q13::17q25----17qter) and a mouse line deficient in thymidine kinase. These hybrids were constantly maintained in HAT selective media in order to select for the presence of the human thymidine kinase gene on the intact chromosome 17 (17q21----22) or the 17/20 (17pter----17q25::20q13----20qter) translocation chromosome. We detected human GAA by rocket immunoelectrophoresis, using a heterologous antibody raised against human acid alpha-glucosidase. A clone which contained the 17/20 translocation and no intact chromosome 17 was still positive for GAA. This finding confirms the exclusion of GAA from 17q25----17qter reported by Nickel et al. (1982). Combined with earlier results (Weil et al. 1979), GAA can be assigned to 17q21----17q25. A clone which contained only the 17/20 translocation chromosome and no intact chromosome 20 contained ADA. This confirms the previous localization of ADA to 20q13.2----qter by gene dosage studies (Philip et al. 1980)
— id: 15215, year: 1984, vol: 48, page: 49, stat: Journal Article,

Murine T cell receptor beta chain is encoded on chromosome 6
Lee NE; D'Eustachio P; Pravtcheva D; Ruddle FH; Hedrick SM; Davis MM
1984 Sep 1;160(3):905-913, Journal of experimental medicine
Southern blot analysis of somatic cell hybrid lines indicates that the beta chain of the T cell receptor for antigen maps to chromosome 6 of the mouse. An experiment testing hybridization of the constant region of this gene to DNA from a hybrid cell line containing a translocation of chromosome 6 supports the localization of this gene to the proximal (centromeric) one-third of chromosome 6, in the same general region as the immunoglobulin kappa chain locus. This may be another indication of the shared evolutionary origins of the genes encoding both T and B cell antigen recognition
— id: 17267, year: 1984, vol: 160, page: 905, stat: Journal Article,

Somatic cell genetics and gene families
D'Eustachio P; Ruddle FH
1983 May 27;220(4600):919-924, Science
The utility of somatic cell genetic analysis for the chromosomal localization of genes in mammals is well established. With the development of recombinant DNA probes and efficient blotting techniques that allow visualization of single-copy cellular genes, somatic cell genetics has been extended from the level of phenotypes expressed by whole cells to the level of the cellular genome itself. This extension has proved invaluable for the analysis of genes not readily expressed in somatic cell hybrids and for the study of multigene families, especially pseudogenes dispersed in different chromosomes throughout the genome
— id: 17272, year: 1983, vol: 220, page: 919, stat: Journal Article,

c-myc Gene rearrangements involving gamma immunoglobulin heavy chain gene switch regions in murine plasmacytomas
Harris LJ; Remmers EF; Brodeur P; Riblet R; D'Eustachio P; Marcu KB
1983 Dec 10;11(23):8303-8315, Nucleic acids research
In murine plasmacytomas, the c-myc gene has frequently been found to undergo rearrangement by virtue of a T(12;15) chromosome translocation. The immunoglobulin heavy chain gene switch region (S alpha) constitutes the target for most of these recombinations particularly in IgA producing plasmacytomas. We sought to identify non-S alpha myc target sites in several IgG producing tumors. The c-myc target in MPC-11 (a BALB/c IgG2b producing plasmacytoma) has been cloned, localized to the Igh-C locus and identified as the gamma 2a heavy chain gene switch region (S gamma 2a). Furthermore, by Southern blot hybridization, we have determined that the S gamma 2b region is the c-myc target in two NZB IgG2b producing plasmacytomas. The potential relation between Ig class expressed and c-myc translocation target is discussed
— id: 17270, year: 1983, vol: 11, page: 8303, stat: Journal Article,

The mouse genome contains two nonallelic pro-opiomelanocortin genes
Uhler M; Herbert E; D'Eustachio P; Ruddle FD
1983 Aug 10;258(15):9444-9453, Journal of biological chemistry
In the anterior pituitary pro-opiomelanocortin (POMC) is the protein precursor to both adrenocorticotropin and beta-lipotropin but in the intermediate pituitary POMC serves as the precursor to alpha-melanocyte-stimulating hormone and beta-endorphin. In addition, POMC expression in the anterior pituitary is inhibited by glucocorticoids but stimulated by corticotropin-releasing factor while POMC expression in the intermediate lobe is not responsive to glucocorticoids but is inhibited by dopamine. In this study we have asked whether tissue-specific processing and regulation of POMC could be related to the presence of more than one POMC gene. We report here that the mouse genome contains two POMC related gene sequences, alpha- and beta-POMC, that alpha-POMC is located on mouse chromosome 12 while beta-POMC is on a different chromosome, probably chromosome 19. Sequencing of phage lambda recombinants containing alpha- and beta-POMC sequences indicated that the alpha-POMC gene in mouse is very similar to the single POMC gene found in human, bovine, and rat genomes. The sequence of the mouse beta-POMC gene is quite different from that of the alpha-POMC gene. One important difference is that the beta-POMC gene has a translation stop signal in place of the first amino acid in beta-endorphin (Tyr). The beta-POMC gene has many features in common with the pseudogene of the beta-globin family
— id: 17271, year: 1983, vol: 258, page: 9444, stat: Journal Article,

Aberrant rearrangement of the kappa light-chain locus involving the heavy-chain locus and chromosome 15 in a mouse plasmacytoma
VanNess BG; Shapiro M; Kelley DE; Perry RP; Weigert M; D'Eustachio P; Ruddle F
1983 Feb 3;301(5899):425-427, Nature
The creation of a functional antibody gene requires the precise recombination of gene segments initially separated on the chromosome. Frequently errors occur in the process, resulting in the formation of a non-functional gene. The non-functional genes can be generated by incomplete rearrangements, frameshifts, or the use of pseudo V or J joining segments. It is likely that these aberrant rearrangements arise by the same mechanism as is used in generating functional genes, a process which we have suggested may involve unequal sister chromatid exchange. Aberrant rearrangements of immunoglobulin genes occur in normal lymphocytes and play a major part in allelic exclusion. However, it has recently been suggested that aberrant rearrangements involving immunoglobulin and non-immunoglobulin genes may be involved in tumorigenesis. This suggestion has been stimulated by the frequent occurrence of translocations involving chromosomes known to carry immunoglobulin genes in B-cell malignancies. The rearrangement of non-immunoglobulin DNA to the heavy-chain locus has recently been reported. Some aberrant rearrangements of the kappa locus appear to be due to rearrangements to sites that do not include the conventional sequence for V gene segment joining. Here we describe an aberrant kappa rearrangement that has led to the joining of DNA from chromosomes 15, 6 and 12, and so appears to be the result of chromosomal translocations or transpositions. As 15/6 or 15/12 translocations have frequently been found in mouse plasmacytomas (as have analogous translocations in human lymphocyte tumours) this aberrant kappa rearrangement may be unique to the plasmacytoma from which it was isolated
— id: 17273, year: 1983, vol: 301, page: 425, stat: Journal Article,

Dispersion of argininosuccinate-synthetase-like human genes to multiple autosomes and the X chromosome
Beaudet AL; Su TS; O'Brien WE; D'Eustachio P; Barker PE; Ruddle FH
1982 Aug;30(1):287-293, Cell
DNA sequences closely homologous to argininosuccinate synthetase are present at ten or more distinct locations in the human genome, including sites on chromosomes 6, 9 and X. Argininosuccinate synthetase thus represents one of the most widely dispersed multigene families described to date, the first instance of a multigene family associated with an enzyme of intermediary metabolism and, perhaps most striking, the first instance of a multigene family with members on both autosomes and sex chromosomes
— id: 17278, year: 1982, vol: 30, page: 287, stat: Journal Article,

Comparative gene mapping: murine lambda light chain genes are located in region cen to B5 of mouse chromosome 16 not homologous to human chromosome 21
Francke U; De Martinville B; D'Eustachio P; Ruddle FH
1982 ;33(3):267-271, Cytogenetics & cell genetics
We have mapped the genes for murine immunoglobulin lambda light chains to the region of chromosome 16 proximal to band B5 by hybridizing a cDNA probe for gamma light chains to the DNA of a series of hybrid clones made between mouse fibroblasts carrying Searle's translocation, T(X;16)16H, and Chinese hamster cells. Based on homology, we predict that the human Ig gamma gene (IGL) will map to the proximal two-thirds of HSA 22
— id: 17283, year: 1982, vol: 33, page: 267, stat: Journal Article,

Chromosomal assignment of the endogenous proto-oncogene C-abl
Goff SP; D'Eustachio P; Ruddle FH; Baltimore D
1982 Dec 24;218(4579):1317-1319, Science
— id: 17274, year: 1982, vol: 218, page: 1317, stat: Journal Article,

Localization of the casein gene family to a single mouse chromosome
Gupta P; Rosen JM; D'Eustachio P; Ruddle FH
1982 Apr;93(1):199-204, Journal of cell biology
A series of mouse-hamster somatic cell hybrids containing a variable number of mouse chromosomes and a constant set of hamster chromosomes have been used to determine the chromosomal location of a family of hormone-inducible genes, the murine caseins. Recombinant mouse cDNA clones encoding the alpha-, beta-, and gamma-caseins were constructed and used in DNA restriction mapping experiments. All three casein cDNAs hybridized to the same set of somatic cell hybrid DNAs isolated from cells containing mouse chromosome 5, while negative hybridization was observed to ten other hybrid DNAs isolated from cells lacking chromosome 5. A fourth cDNA clone, designated pCM delta 40, which hybridized to an abundant 790 nucleotide poly(A)RNA isolated from 6-d lactating mouse mammary tissue, was also mapped to chromosome 5. The chromosomal assignment of the casein gene family was confirmed using a mouse albumin clone. The albumin gene had been previously localized to mouse chromosome 5 by both breeding studies and analogous molecular hybridization experiments. An additional control experiment demonstrated that another hormone-inducible gene, specifying a 620 nucleotide abundant mammary gland mRNA, hybridized to DNA isolated from a different somatic cell hybrid line. These studies represent the first localization of a peptide and steroid hormone-responsive gene family to a single mouse chromosome
— id: 17280, year: 1982, vol: 93, page: 199, stat: Journal Article,

DNA sequence associated with chromosome translocations in mouse plasmacytomas
Harris LJ; D'Eustachio P; Ruddle FH; Marcu KB
1982 Nov;79(21):6622-6626, Proceedings of the National Academy of Sciences of the United States of America
A DNA sequence that generates aberrantly rearranged immunoglobulin heavy chain constant region genes in murine plasmacytomas is shown to participate in a chromosome translocation. We have previously termed this DNA sequence NIARD for non-immunoglobulin-associated rearranging DNA. NIARD rearrangements were found frequently in murine plasmacytomas but were not detected in normal lymphocytes. These rearrangements occasionally involve the switch region of the C alpha gene. In this study, DNA samples obtained from mouse-Chinese hamster somatic cell hybrid lines were digested with various restriction endonucleases and analyzed by the Southern transfer technique with a NIARD hybridization probe. These experiments show that NIARD resides on chromosome 15 in the mouse germ line. Since NIARD is found adjacent to the C alpha gene (located on chromosome 12) in some plasmacytomas, it is apparent that a translocation involving these two chromosomes has occurred. We have proposed a rcpT(12;15) model to explain our data. The implications of NIARD rearrangements for malignant transformation are discussed
— id: 17276, year: 1982, vol: 79, page: 6622, stat: Journal Article,

Structural genes of the mouse major urinary protein are on chromosome 4
Krauter K; Leinwand L; D'Eustachio P; Ruddle F; Darnell JE
1982 Aug;94(2):414-417, Journal of cell biology
The major urinary proteins (MUPs) of mouse are a family of at least three major proteins which are synthesized in the liver of all strains of mice. The relative levels of synthesis of these proteins with respect to each other in the presence of testosterone is regulated by the Mup-a locus located on chromosome 4. In an effort to determine the mechanism of this regulation in molecular terms, a cDNA clone containing most of the coding region of a MUP protein has been isolated and identified by partial DNA sequence analysis. Using a combination of hybridization analysis and somatic cell genetics, the structural gene family has been unambiguously mapped to mouse chromosome 4. These data suggest that Mup-a regulation operates in a cis fashion and that models proposing trans regulation of MUP protein synthesis are unlikely
— id: 17277, year: 1982, vol: 94, page: 414, stat: Journal Article,

Chromosomal location of a human alpha interferon gene family
Slate DL; D'Eustachio P; Pravtcheva D; Cunningham AC; Nagata S; Weissmann C; Ruddle FH
1982 Apr 1;155(4):1019-1024, Journal of experimental medicine
To determine the chromosomal location of the human alpha interferon genes, we scored a series of human/rodent somatic cell hybrids for the presence of DNA sequences hybridizing to an alpha 1 interferon DNA probe. The presence of human chromosome 9 in a hybrid correlated with the presence of a family of alpha interferon genes
— id: 17281, year: 1982, vol: 155, page: 1019, stat: Journal Article,

Chromosomal localization of the Moloney sarcoma virus mouse cellular (c-mos) sequence
Swan D; Oskarsson M; Keithley D; Ruddle FH; D'Eustachio P; Vande Woude GF
1982 Nov;44(2):752-754, Journal of virology
The Moloney sarcoma virus-specific onc gene, referred to as v-mos, was used as probe to hybridize to restricted DNAs from various mouse-Chinese hamster hybrid cell lines. These hybrid cells contain, in addition to all of the Chinese hamster chromosomes, various numbers (less than a full complement) of mouse chromosomes. Comparison of the presence or absence of the mouse cellular mos gene with the known karyotype in each of the hybrid cell lines allows us to conclude that the mos gene is on mouse chromosome 4
— id: 17275, year: 1982, vol: 44, page: 752, stat: Journal Article,

J chain is encoded by a single gene unlinked to other immunoglobulin structural genes
Yagi M; D'Eustachio P; Ruddle FH; Koshland ME
1982 Mar 1;155(3):647-654, Journal of experimental medicine
Immunoglobulin J chain mediates the polymerization of both IgM and IgA immunoglobulins. Its synthesis is closely regulated in B lymphocytes, apparently at the level of RNA transcription. To define the genetic bases of this regulation, we have determined the location and number of J chain genes in the mouse. Analysis of DNA from a group of somatic cell hybrids containing various mouse chromosomes on a constant background of Chinese hamster chromosomes indicated that this gene is located on mouse chromosome 5, unlinked to immunoglobulin heavy and light chain structural genes. Restriction mapping experiments further suggested the existence of a single J chain gene per haploid genome. This result was confirmed by quantitative analyses of band intensities yielded by Southern blots of mouse genomic DNA and J gene-containing plasmid DNA
— id: 17282, year: 1982, vol: 155, page: 647, stat: Journal Article,

Immunoglobulin heavy chain gene rearrangement and transcription in murine T cell hybrids and T lymphomas
Zuniga MC; D'Eustachio P; Ruddle NH
1982 May;79(9):3015-3019, Proceedings of the National Academy of Sciences of the United States of America
We have examined the arrangement of immunoglobulin heavy chain constant (CH) and joining (JH) region genes in murine T cell hybrid lines and in T lymphomas. CH genes derived from both parental cell types were present in all hybrids for which polymorphism in sequences flanking CH genes permitted us to distinguish parental CH genes. All T lymphomas and T cell hybrids retained the C alpha gene in germ-line configuration and all but one cell line had germ-line C mu genes. Novel DNA fragments reactive with JH probes were observed in six of nine T cell hybrids, as well as in two T lymphomas, WEHI7.1 and YAC-1, but not in the fusion parent, BW5147. No RNA homologous to C gamma 2b, C alpha, or lambda genes was detected in any of the T cell lines. T cell lines contained poly(A)+ RNA homologous to a C mu cDNA probe. More importantly, in several cell lines the C mu RNAs were associated with membrane-bound polyribosomes. These results suggest that both JH rearrangements and C mu RNA production occur in at least some mature, antigen-specific T cells. They may therefore reflect events in normal T cell development and function related to those involved in the generation of the T receptor for antigen
— id: 17279, year: 1982, vol: 79, page: 3015, stat: Journal Article,

Chromosomal location of structural genes encoding murine immunoglobulin lambda light chains. Genetics of murine lambda light chains
D'Eustachio P; Bothwell AL; Takaro TK; Baltimore D; Ruddle FH
1981 Apr 1;153(4):793-800, Journal of experimental medicine
To determine the chromosomal localization of murine lambda light (L) chain structural genes, DNA from a panel of 11 mouse x hamster somatic cell hybrids was scored for the presence of sequences homologous to cloned lambda DNA probe molecules. Six of the hybrids had detectable lambda I and lambda II gene sequences. In all six, the full complement of murine sequences was present, and in its germline configuration. The remaining hybrids lacked any detectable murine lambda L chain gene sequences. The only mouse chromosome present in all of the positive hybrids and absent from the negative ones was number 16, allowing the assignment of lambda L chain structural genes to this chromosome. Together with the previous assignments of the kappa L chain genes to chromosome 6 and heavy chain genes to chromosome 12, this finding completes the mapping of Ig structural genes in the mouse at the chromosomal level
— id: 17288, year: 1981, vol: 153, page: 793, stat: Journal Article,

Murine alpha-fetoprotein and albumin: two evolutionarily linked proteins encoded on the same mouse chromosome
D'Eustachio P; Ingram RS; Tilghman SM; Ruddle FH
1981 May;7(3):289-294, Somatic cell genetics
Several lines of evidence suggest a close functional relationship and a common evolutionary origin for alpha-fetoprotein and albumin. In the mouse, breeding studies have previously allowed the assignment of the albumin gene to chromosome 5. To test the possible linkage of alpha-fetoprotein and albumin, five somatic cell hybrids containing various combinations of mouse chromosomes, together with a constant set of hamster chromosomes, were tested for the presence of both genes using DNA restriction mapping techniques. Two of the five hybrids possessed both genes, and the other three lacked both. The only mouse chromosome present in the positive lines and absent from the negative ones was number 5, allowing the assignment of both genes to this chromosome
— id: 17287, year: 1981, vol: 7, page: 289, stat: Journal Article,

Chromosomal distribution of ribosomal protein genes in the mouse
D'Eustachio P; Meyuhas O; Ruddle F; Perry RP
1981 May;24(2):307-312, Cell
The chromosomal distributions of five families of mouse r-protein genes (S16, L18, L19, L30 and L32/33) were studied by Southern blot analysis of DNa from a panel of mouse-hamster hybrid cells containing various complements of mouse chromosomes. Our results indicated that members of a particular family are often located on more than one chromosome, that extensive clustering of many r-protein gene families on a few chromosomes is unlikely, and that there is no obligatory linkage of r-protein and rRNA genes
— id: 17286, year: 1981, vol: 24, page: 307, stat: Journal Article,

Human nucleolus organizers on nonhomologous chromosomes can share the same ribosomal gene variants
Krystal M; D'Eustachio P; Ruddle FH; Arnheim N
1981 Sep;78(9):5744-5748, Proceedings of the National Academy of Sciences of the United States of America
The distributions of three human ribosomal gene polymorphisms among individual chromosomes containing nucleolus organizers were analyzed by using mouse--human hybrid cells. Different nucleolus organizers can contain the same variant, suggesting the occurrence of genetic exchanges among ribosomal gene clusters on nonhomologous chromosomes. Such exchanges appear to occur less frequently in mice. This difference is discussed in terms of the nucleolar organization and chromosomal location of ribosomal gene clusters in humans and mice
— id: 17285, year: 1981, vol: 78, page: 5744, stat: Journal Article,

Dispersion of alpha-like globin genes of the mouse to three different chromosomes
Leder A; Swan D; Ruddle F; D'Eustachio P; Leder P
1981 Sep 17-23;293(5829):196-200, Nature
— id: 17284, year: 1981, vol: 293, page: 196, stat: Journal Article,

Chromosomal location of the structural gene cluster encoding murine immunoglobulin heavy chains
D'Eustachio P; Pravtcheva D; Marcu K; Ruddle FH
1980 Jun 1;151(6):1545-1550, Journal of experimental medicine
To determine the chromosomal location of mouse immunoglobulin heavy chain structural genes unambiguously, a panel of somatic cell hybrids was scored for the presence of DNA sequences homologous to gamma 2b-, mu-, and alpha-heavy chain-constant region DNA probe molecules. The hybrids, formed between mouse and hamster cells, contained various combinations of mouse chromosomes plus a full set of hamster chromosomes. Hybrids that retained mouse chromosome 12 reacted with the probes, whereas hybrids that had lost the chromosome, or its distal half, failed to react. These results indicate that structural genes for the gamma 2b-, mu-, and alpha-heavy chain-constant regions map to the distal half of this chromosome
— id: 17289, year: 1980, vol: 151, page: 1545, stat: Journal Article,

Somatic cell genetics and the development of the immune system
D'Eustachio P; Ruddle FH
1980 ;14(Pt 2):59-96, Current topics in developmental biology
— id: 17290, year: 1980, vol: 14, page: 59, stat: Journal Article,

Chromosomal assignment of the mouse kappa light chain genes
Swan D; D'Eustachio P; Leinwand L; Seidman J; Keithley D; Ruddle FH
1979 Jun;76(6):2735-2739, Proceedings of the National Academy of Sciences of the United States of America
Mouse-hamster somatic cell hybrids containing a variable number of mouse chromosomes have been used in experiments to determine which mouse chromosome carries the immunoglobulin kappa light chain genes. It has been shown by nucleic acid hybridization that the kappa constant gene and the genes for at least one variable region subgroup are on mouse chromosome 6. This somatic cell genetic mapping procedure appears to be general and can be applied to any expressed or silent gene for which an appropriate nucleic acid probe exists
— id: 17291, year: 1979, vol: 76, page: 2735, stat: Journal Article,

The specific antigen-binding cell populations of individual fetal mouse spleens: repertoire composition, size, and genetic control
Cohen JE; D'Eustachio P; Edelman GM
1977 Aug 1;146(2):394-411, Journal of experimental medicine
— id: 17292, year: 1977, vol: 146, page: 394, stat: Journal Article,

Clonal selection and the ontogeny of the immune response
D'Eustachio P; Rutishauser US; Edelman GM
1977 ;74(5):1-60, International review of cytology. Supplement
— id: 17294, year: 1977, vol: 74, page: 1, stat: Journal Article,

Surface signals and cellular regulation of growth
Edelman GM; D'Eustachio P; McClain DA; Jazwinski SM
Mitosis facts and questions Berlin, Springer, 1977,
— id: 2591, year: 1977, vol: , page: 20, stat: Chapter,

Role of surface modulating assemblies in growth control of normal and transformed fibroblasts
McClain DA; D'Eustachio P; Edelman GM
1977 Feb;74(2):666-670, Proceedings of the National Academy of Sciences of the United States of America
Cellular microtubules, microfilaments, and surface receptors have been postulated to form a surface modulating assembly that regulates surface receptor mobility and cell growth. To test this hypothesis, we examined three agents known to affect cell growth [colchicine, concanavalin A (Con A), and the src gene product of Rous sarcoma virus] for their effects on chick embryo fibroblasts. Individual cells from serum-starved normal fibroblast populations became committed to enter S phase at various times over a 12 hr period after exposure to serum. Colchicine and other microtubule-disrupting agents blocked entry into S phase at a point close to the commitment point for each cell. The lectin Con A also blocked entry into the S phase when present in doses sufficient to modulate surface receptor mobility. In contrast, succinyl-Con A, which does not induce surface modulation, had no effect. Both Con A and colchicine blocked the appearance of cytoplasmic factors capable of stimulating DNA replication in a cell-free system. To study endogenous effects on the surface modulating assembly, we infected fibroblasts with a Rous sarcoma virus (tsNY68) having a temperature-sensitive mutation in the transforming (src) gene. We have previously shown that microtubular and microfilamentous structures of the surface modulating assembly are direct or indirect targets of the src gene product with consequent reduction in the capacity of Con A to induce surface modulation. TsNY68-infected fibroblasts shifted to the non-permissive temperature acquired normal microtubular morphology more rapidly (2 hr) than cells grown at the permissive temperature in the presence of protein synthesis inhibitors (7.5 hr). This suggests that the src gene product acts directly on the surface modulating assembly rather than via the nucleus or at the level of protein synthesis. Furthermore, 'transformation' of the surface modulating assembly was partly blocked by treatment of the infected cells with Con A but not succinyl-Con A. Both Con A and colchicine inhibited entry into the S phase following a shift from nonpermissive to permissive growth conditions. All of these observations are in accord with the hypothesis that the surface modulating assembly acts as a signal regulator in growth control
— id: 17293, year: 1977, vol: 74, page: 666, stat: Journal Article,

Variation and control of specific antigen-binding cell populations in individual fetal mice
D'Eustachio P; Cohen JE; Edelman GM
1976 Jul 1;144(1):259-265, Journal of experimental medicine
To determine the extent and nature of individual variation in the development of specific antigen-binding cells, the numbers of cells specific for each of two antigens in the spleens of individual random-bred Swiss-L and inbred CBA/J and BALB/c fetal mice were measured as a function of spleen size. For Swiss-L fetuses, the ratio of antigen-binding cells to nucleateated cells varied more than would arise from sampling fluctuation. For each inbred strain, however, the number of cells specific for a given antigen was a constant proportion of the total number of nucleated cells within sampling error. These proportions varied from antigen to antigen, and from strain to strain. The ratio of the proportions of cells specific for the two antigens, however, differed no more from CBA/J to BALB/c mice than would be expected in repeated samples of cells from the spleen of a single fetus. These results confirm at the level of the individual fetus the uniform pattern of development seen for populations of fetuses. They reveal a surprising precision in the proliferation of specific antigen-binding cell populations and suggest that the development of these cells may be subject to strong genetic controls
— id: 17295, year: 1976, vol: 144, page: 259, stat: Journal Article,

Frequency and avidity of specific antigen-binding cells in developing mice
D'Eustachio P; Edelman GM
1975 Nov 1;142(5):1078-1091, Journal of experimental medicine
In order to analyze the development of antibody diversity in which the genes coding for the antigen-specific cells we have compared the binding of diverse antigens by cells in the fetal, neonatal, and adult mouse. Although the numbers of antigen-binding cells present in fetuses and young animals were smaller than in adults, no restriction could be detected in the varity of specificities expressed in the fetuses, either with respect to the kinds of antigens bound, or to the range of avidities of binding. Cells specific for each of the 11 antigens tested could be detected in the fetus only in the last 4 days before birth, at which time they appeared both in the liver and in the spleen. In all cases, these cells disappeared both in the liver and in the spleen. In all cases, these cells disappeared from the liver within a day of birth, but continued to increase in number in the spleen until adulthood
— id: 17296, year: 1975, vol: 142, page: 1078, stat: Journal Article,

Immunological functions of lymphocytes fractionated with antigen-derivatized fibers
Rutishauser U; D'Eustachio P; Edelman GM
1973 Dec;70(12):3894-3898, Proceedings of the National Academy of Sciences of the United States of America
— id: 17297, year: 1973, vol: 70, page: 3894, stat: Journal Article,

Fb, a ndw enzymatic fragment of human G immunoglobulin
Gall WE; D'Eustachio P
1972 Nov 21;11(24):4621-4628, Biochemistry
— id: 17298, year: 1972, vol: 11, page: 4621, stat: Journal Article,