PRODUCTION AND MAINTENANCE OF H-2 MUTATIONS

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This project has two basic objectives. The first is to conduct a final screening program specifically aimed at the recovery of H-2 mutations which can answer basic questions about the process(es) which have been implicated in their generation. The second is to continue meeting requests from other investigators for mutants and, over the course of the project period, to phase out the active breeding and culminate with the preservation of the mutants in a frozen embryo bank. Most, if not all, of the in vivo H-2 mutations have characteristics which have been interpreted to imply their generation via a process involving transfers of DNA sequences between non-allelic genes (micro-recombination or "gene conversion" rather than relying on simply the accretion of single base changes. One of the basic pieces of information missing for the modeling/testing of such a process is whether such transfers can definitively be attributed to cis-(within-single chromosomes) or trans (between homologous chromosomes) configurations. This project proposes a limited and directed screening program to attempt to identify H-2 mutation-s which can definitively be attributed to cis or to trans "gene conversions". Such an search is unlikely to occur elsewhere. Actual demonstration of such events will facilitate the analysis of this process which is thought by many to be important in the in vivo generation of diversity within the MHC. This project also proposes to continue the maintenance of a colony of mice bearing H-2 histocompatibility gene mutations as a resource colony. New mutants may be added, if and as they become available. Maintained strains will be systematically monitored by skin grafting to ensure their genetic integrity. The current frequency of requests suggests that an actively breeding colony is still justifiable to expeditiously fulfill the requests. However the phasing out of the breeding colony, and its entry into a frozen embryo bank(s), is planned in order to accommodate the P.I.'s future plans.