Introduction to the Workshop
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The electronic form of this document may be cited in the following style:
Human Genome Program, U.S. Department of Energy, DOE Human Genome Program Contractor-Grantee Workshop IV, 1994.
Abstracts scanned from text submitted for November 1994 DOE Human Genome Program Contractor-Grantee Workshop. Inaccuracies have not been corrected.
FUNCTIONAL ANALYSIS OF GENES USING THE MOUSE AS A MODEL SYSTEM
Peter R. Hoyt, Theresa A. Banks[2*], Christopher Bartholomew, Patrick J. Blair, Virginia L. Godfrey, Marilyn K. Kerley, William H. Lee, Brigid L. M. Hogan, Barry T. Rouse, James N. Ihle, S.Steven Potter, and Michael L. Mucenski[4,8]
University of Tennessee-Oak Ridge Graduate School of Biomedical Sciences, PO Box 2009, Oak Ridge, Tennessee 37831-8080 USA,, Department of Microbiology, University of Tennessee, Knoxville, TN 37996 USA, Beatson Institute for Cancer Research, Glasgow G611 BD Scotland, Biology Division, Oak Ridge National Laboratory, PO Box 2009, Oak Ridge, TN 37831-8080 USA, Department of Cell Biology, Vanderbilt University Medical School, Nashville, TN 37232-217 USA, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105 USA, Institute of Developmental Research, Children's Hospital Research Foundation, Cincinnati, Ohio 45229 USA, Corresponding Author.
It has been shown that murine and human genomes are considerably conserved at the nucleic acid and gene linkage levels. These similarities make the mouse an excellent model for the physical and functional mapping of the human genome. As the murine homologues of interesting human genes are identified, we will use targeted mutagenesis technology of embryonic stem (ES) cells to generate mice so that the biological function of these genes may be determined. In the course of these studies, murine models for human diseases will be emphasized.
Our targeted mutagenesis laboratory has already generated null mutants for two genes which are evolutionarily conserved between mice and humans, the proto-oncogene Evi-1, and the cytokine tumor necrosis factor-beta (TNF-ß), which is also referred to as lymphotoxin-alpha (LT-alpha). Detailed characterization of the homozygous mutant animals will be presented. The Evi-1 gene appears to play a critical role in the development of multiple organ systems while LT-alpha functions in the development of secondary lymphoid organs in the mouse. These results show the utility of targeted mutagenesis technology which will enable us to determine the biological function of the murine homologues of human genes that may be involved in specific disease states. Future work will involve the analysis of genes identified through the physical mapping of the mouse genome within well defined mouse-human homology regions, a collaborative effort between the Mammalian Genetics and Development Section of the Biology Division of the Oak Ridge National Laboratory and the Human Genome Center of the Lawrence Livermore National Laboratory.
This work is supported by the USDOE under contract DE-AC05840R21400 with Martin Marietta Energy Systems, Inc.
*Present Address: Viagene, Inc., San Diego, CA 92121-1204