GENETIC ASPECTS OF VIRAL ONCOGENESIS IN WILD MOUSE SPECIES

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A number of mouse chromosomal genes have been described which affect the susceptibility of mice to retrovirus-induced neoplastic disease. These genes include endogenous retroviral sequences, mouse cellular genes which facilitate or restrict virus replication, and proto- oncogenes disrupted by viral insertion. In the process of characterizing new common viral insertions in tumors induced by Abelson and Moloney MuLVs, we identified two new integration sites on the same chromosome, Chromosome 10. We defined the close genetic and physical distance between these insertion sites and the previously described oncogene Myb on this Chromosome, but suggest that these insertions may disrupt other oncogenic sequences in this region. In other experiments, we began analysis of several crosses involving DBA/2J mice which carries a locus responsible for resistance to MCF subtype of viruses, Rmcf. We defined the genetic map location of Rmcf, we identified an additional resistance gene in these same crosses which maps to Chr 1, and we are following inheritance of Rmcf through serial backcrosses to M. castaneus which lacks endogenous MCF viruses. These experiments should help determine whether Rmcf represents an endogenous provirus expression of which blocks viral cell surface receptors. Finally, we used a fragment of the recently clone amphotropic viral cell surface receptor to map the mouse gene to Chromosome 8.