GENETIC ASPECTS OF VIRAL ONCOGENESIS IN WILD MOUSE SPECIES

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Various mouse chromosomal genes alter the susceptibility of mice to retrovirus-induced neoplastic disease. These genes include endogenous retroviral sequences as well as mouse cellular genes which facilitate or restrict virus replication. We have identified a novel common viral integration region associated with tumor induction by type-B leukemogenic retrovirus. This virus is related to mouse mammary tumor virus, but induces T-cell thymic lymphomas. A novel virus integration site was identified in 20% of the tumors screened, suggesting the presence of a functional gene involved in tumor induction. This gene was mapped to a site on the X chromosome not previously known to contain protooncogene sequences. Other experiments were designed to follow the genetic linkage of loci responsible for the clonal deletion of self-Mlsf reactive T cells. Results from these investigations indicated that at least three known MMTV proviruses, Mtv-8, -9, and -11 are responsible for this deletion.