GENETIC ASPECTS OF VIRAL ONCOGENESIS IN MICES

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Genetic studies on virus-induced neoplastic disease have led to the identification of many chromosomal genes involved in these processes. Many mouse genes affecting susceptibility to virus or virus-induced disease have been identified in the various inbred laboratory strains, and we have expanded these studies to include wild mouse populations because of their greater genetic diversity. We have identified and characterized a novel wild mouse virus, HoMuLV, isolated from Eastern European mice. This virus is pathogenic, has ecotropic host range despite its different envelope gene, and also differs from other murine leukemic viruses in its gag gene. In other experiments, we characterized the novel oncogenic sequence transduced by a defective pathogenic wild mouse virus. Two copies of this oncogene were identified in the mouse genome, one of which is a pseudogene. We also demonstrated that activation of the Harvey ras oncogene was associated with the development of a T cell leukemia and that this activation was accomplished by viral integration and chromosomal rearrangement. Finally, we positioned the gene encoding the ecotropic MULV cell surface receptor and characterized a related genomic sequence which may represent the amphotropic MuLV receptor gene.