PRODUCTION AND ANALYSIS OF HISTOCOMPATIBILITY MUTANTS

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This project seeks to maintain, to develop and to expand a colony of mice which carry mutations of genes which affect skin graft transplantation. A substantial number of lines are already on hand, completed or under development. These include strains bearing H-2 mutations as well as non-H-2 gene mutations. New mutations will be sought by screening the progeny of ENU-treated or untreated male mice of strains C57BL/6Kh and BALB/cKh. In addition a number of other inbred, congenic and recombinant strains will be continually screened as part of a system to monitor their genetic integrity and mutants may be recovered from them as well. Mutants will be entered into immunogenetic analyses, both as part of formal collaborative efforts and by making them available to other investigators upon request. The formal collaborations include Dr. Stanley Nathenson (biochemical and structural analysis of mutant gene products at the protein and DNA levels), Dr. Ian McKenzie (serological analyses of mutant gene products), Dr. Kees Melief (functional consequences of the mutations for cell-mediated assays such as CML, MLR and MHC restriction), Dr. Peter Wettstein (looking for changes in integrated viral sequences as a result of mutations involving mutations of non-H-2 genes), and Dr. Byung Kim (assisting in electrophoretic techniques). We will be specifically examining the recently reovered H-2dm6 mutation (which has lost Dd, but retained Ld and apparently Rd as well) to see if D region products other than D,L and R can be identified which are missing in the mutant. We also propose attempting to raise alloantisera against some of the minor histocompatibility mutants as a step toward future analyses of these genes.