The NHLBI-Bay Area Functional Genomics Consortium will use gene-trap vectors to inactivate thousands of genes in mouse embryonic stem (ES) cells and make them freely available for the purpose of generating knockout mice. In preliminary studies, custom gene-trap vectors have been used to trap more than 500 mouse genes, some completely novel, and many corresponding to ESTs of unknown function. Approximately 150 of the """"""""trapped"""""""" ES cell clones have been transmitted through the germline, and studies of the knockout mice have already led to the identification of completely novel genes that are important in cardiopulmonary development and disease. The Consortium involves several leading San Francisco Bay Area research institutions: The J. David Gladstone Institutes, the University of California, San Francisco, and the University of California, Berkeley. The Consortium is organized into nine Components: (1) Gene Trapping in Embryonic Stem Cells, (2) Computational Methods for Predicting Gene Function, (3) In Situ Hybridization, (4) Gene Expression Profiling and Analysis, (5) Mouse Resource for Pulmonary Disease, (6) Mouse Resource for Lipid Metabolism and Atherogenesis, (7) Mouse Resource for Cardiopulmonary Development, (8) Cardiopulmonary Genomics Education, and (9) Administration. The major objective of the Consortium (corresponding to Component 1) is to use custom gene-trap vectors to inactivate at least 2,500 genes per year in ES cells. Each """"""""trapped"""""""" ES cell line will be posted on the Consortium's website (genetrap.org) and will be distributed freely to the research community for the purpose of producing knockout mice. A second objective (corresponding to Components 2-4) is to assess which of the ES cell lines is likely to be valuable for understanding cardiopulmonary development and common cardiopulmonary diseases. To achieve this objective, the investigators will use computational approaches, expression profiling with DNA microarrays, and in situ hybridization studies. A third objective (corresponding to Components 5-7) is to select a few ES cell clones for the production of knockout mice, for the purpose of understanding genes involved in cardiopulmonary development and disease. The Consortium's resources will be distributed freely to any interested investigator and should provide a catalyst for many different NHLBI-funded research programs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL066621-04
Application #
6619736
Study Section
Special Emphasis Panel (ZHL1-CSR-L (S2))
Program Officer
Banks-Schlegel, Susan P
Project Start
2000-09-30
Project End
2004-09-01
Budget Start
2003-08-01
Budget End
2004-09-01
Support Year
4
Fiscal Year
2003
Total Cost
$1,395,347
Indirect Cost
Name
J. David Gladstone Institutes
Department
Type
DUNS #
099992430
City
San Francisco
State
CA
Country
United States
Zip Code
94158
Vergnes, Laurent; Chin, Robert G; de Aguiar Vallim, Thomas et al. (2016) SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression. J Lipid Res 57:410-21
Taglieri, Domenico M; Johnson, Keven R; Burmeister, Brian T et al. (2014) The C-terminus of the long AKAP13 isoform (AKAP-Lbc) is critical for development of compensatory cardiac hypertrophy. J Mol Cell Cardiol 66:27-40
Vergnes, Laurent; Chin, Robert; Young, Stephen G et al. (2011) Heart-type fatty acid-binding protein is essential for efficient brown adipose tissue fatty acid oxidation and cold tolerance. J Biol Chem 286:380-90
Emig, Dorothea; Salomonis, Nathan; Baumbach, Jan et al. (2010) AltAnalyze and DomainGraph: analyzing and visualizing exon expression data. Nucleic Acids Res 38:W755-62
Salomonis, Nathan; Schlieve, Christopher R; Pereira, Laura et al. (2010) Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation. Proc Natl Acad Sci U S A 107:10514-9
Kita-Matsuo, Hiroko; Barcova, Maria; Prigozhina, Natalie et al. (2009) Lentiviral vectors and protocols for creation of stable hESC lines for fluorescent tracking and drug resistance selection of cardiomyocytes. PLoS One 4:e5046
Salomonis, Nathan; Nelson, Brandon; Vranizan, Karen et al. (2009) Alternative splicing in the differentiation of human embryonic stem cells into cardiac precursors. PLoS Comput Biol 5:e1000553
Beigneux, Anne P; Gin, Peter; Davies, Brandon S J et al. (2008) Glycosylation of Asn-76 in mouse GPIHBP1 is critical for its appearance on the cell surface and the binding of chylomicrons and lipoprotein lipase. J Lipid Res 49:1312-21
Weinstein, Michael M; Yin, Liya; Beigneux, Anne P et al. (2008) Abnormal patterns of lipoprotein lipase release into the plasma in GPIHBP1-deficient mice. J Biol Chem 283:34511-8
Gin, Peter; Yin, Liya; Davies, Brandon S J et al. (2008) The acidic domain of GPIHBP1 is important for the binding of lipoprotein lipase and chylomicrons. J Biol Chem 283:29554-62

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