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.There are 5 host range subgroups of murine leukemia viruses (MLVs). Each of these subgroups enters mouse cells following binding to specific cell surface receptors. We collaborated with the laboratory of David Kabat to clone and characterize the receptor for the polytropic subgroup of MLVs. This gene, Rmc1, encodes a 696 amino acid protein with multiple membrane spanning domains. The gene maps to distal mouse Chromosome 1. Allelic variants of this gene act as a receptor for the xenotropic subgroup of MLVs. Our previous studies demonstrated that the wild mouse species M. castaneus is uniquely resistant to polytropic viruses and that this resistance is due to the presence of an altered version of the cell surface receptor. More recent genetic crosses now indicate that two additional genes in the wild mouse genetic background collaborate with Rmc1 to produce this resistance. Immunological assays indicate that these additional genes are likely to represent endogenous viral envelope genes that can interfere with receptor function.We continued to investigate the viral resistance gene, Rmcf, which is responsible for partial resistance to the polytropic class of leukemia viruses. We have transferred this resistance to a wild mouse genetic background by serial backcrossing and used these partial congenics to identify a tightly linked chromosomally integrated copy of the viral envelope. This viral envelope is a candidate for resistance that may function by blocking cell surface viral receptors. We are working on the cloning of this gene (Jung).We are also characterizing a serum factor found in most mice which inactivates leukemia viruses. We have shown that this factor does not inactivate viruses of the ecotropic and amphotropic host range groups, but that it strongly inactivates polytropic viruses and, less strongly, xenotropic viruses. We have determined that the presence of this factor is under single gene control and we have initiated a genome scan to identify the responsible locus (Adamson). We have identified a possible genetic linkage and we are now screening potential candidate genes known to map to this region. - Polytropic leukemia virus, virus receptor, resistance genes, serum neutralizing factor, M. castaneus