MOLECULAR REGULATION OF IMMUNOGLOBULIN GENE EXPRESSION

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Genes encoded on mouse chromosome 12 are central to the regulated development of the immune system. These include the immunoglobulin heavy chain genes themselves, as well as markers of T cells and at least one class of tumor cells. These genes have been widely studied, not only because of their relevance to immune function, but because they provide a powerful model system for the molecular genetic analysis of developmental processes in a mammalian system. Here, we propose to use a combination of recombinant DNA technology with somatic cell genetics to systematically define additional genetic markers of mouse chromosome 12, and to begin to define possible functions for these genes. Specifically, recombinant DNA techniques will be used to clone genomic DNA fragments derived from the chromosome. DNA polymorphisms defined with these fragments will be used to extend and fill in the Mendelian and physical maps of the chromosome. Filter hybridization techniques will be used to identify these cloned DNA fragments that are expressed at the RNA level in particular tissues and at particular stages in lymphocyte development.