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.
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