Genetic Aspects: Viral Oncogenesis In Wild Mouse Species

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Abstract

The various wild mice and inbred strains differ from one another in their susceptibility to retroviruses and retrovirus-induced diseases. These differences are due to allelic differences in specific mouse chromosomal genes, and we have been engaged in an ongoing effort to identify and characterize the mouse genes involved in this resistance. This year, we have been characterizing a serum lipoprotein factor found in most mice that inactivates leukemia viruses. We have determined that the presence of this factor is under control of a single gene that maps to distal mouse Chromosome 10. We have noted its close physical linkage to a good candidate gene, apolipoprotein F, and we have evaluated ApoF as a possible candidate for this serum factor. In another study, we have also continued our efforts to characterize the resistance gene Rmcf, which is responsible for partial resistance to the polytropic class of MLVs. We have now cloned a chromosomally integrated copy of the viral envelope associated with the Rmcf locus, and sequence analysis of this gene indicates it is identical to an unusual viral envelope glycoprotein previously detected in the Rmcf positive strain DBA mice. This suggests Rmcf resistance may be mediated through an interference mechanism. We have also initiated a study to examine the chromosomally integrated copies of leukemia virus genes found in wild mice. We have introduced Moloney leukemia virus into these mice and recovered viruses with novel growth properties. We are in the process of sequencing these recovered recombinant viruses to determine the basis for their unusual properties. Finally, we have collaborated with Dr. J. Dudley on TBLV, a mammary tumor virus derivative that induces lymphomas. We demonstrated that tumor induction is associated with virus insertion near the oncogene myc, but that insertion occurs at a location distinct from that of the lymphoma unducing leukemia viruses.