The goal of this project is to identify murine retroviral gene products that are expressed during development and their possible role in resistance to retrovirus-induced diseases. Using a panel of monoclonal antibodies derived from mice undergoing graft-versus-host disease, we have identified a group of endogenous gp70 molecules expressed both in embryonic and adult tissues. One of these molecules is expressed by secondary embryo cultures derived from mice expressing the resistance allele of the Rmcf locus, a gene which restricts the replication of recombinant MCF viruses in vitro. This gp-70 exhibits an epitope unique to gp70 of MCF viruses. A second gp70 molecule which is expressed by the same cells derived from Rmcf-S mice resembles serologically that of xenotropic viruses. We have now carried out backcross analysis of progeny from (Rmcf-r X Rmcf-S) X Rmcf-S mice and found that restreiction of MCF virus replication (Rmcf-r) segregated with the endogenous MCF but not the xenotropic gp70. The genes encoding these two gp70 molecules are allelic and their expression appears to be coordinately regulated during embryonic development. Expression has been detected in a subpopulation of cells of the erythroid lineage in fetal liver. In the adult these proteins are virtually undetectable unless erythropoiesis is stimulated. Lymphoid cells in adult hematopoietic organs express a third gp70 which is related to that of xenotropic viruses but is serologically distinguishable from the xenotropic gp70 found on embryonic cells. Since we now have antibodies which distinguish the two alleles of the Rmcf gene, we are carrying out backcross analyses to determine whether resistance to retrovirus induced erythroleukemia segregates with one of the endogenous gp70 alleles.
