The goal of this research is to determine the role of recombinant retroviruses inmurine thymic leukemia. These viruses are produced via recombination of ecotropic virus with endogenous virus-related sequences during the preleukemic period. In certain instances, the recombinant viruses are leukemogenic whereas the parental viruses are not. We have now identified an endogenous gene product which is structurally related to the endogenous sequences present in oncogenic recombinant retroviruses. This molecule, termed 81-TAg is specifically expressed on Peanut agglutinin positive blast cells of the thymus of all mouse strains examined. Furthermore, all spontaneous thymic leukemias are positive for 81-TAg. It is thus our goal to determine if the inappropriate expression of these sequences are responsible for transformation. We will clone this gene product using the lambdagtll expression vector system which will allow us to select clones by using a highly specific antibody probe. We will subsequently perform nucleotide sequencing of the 81-TAg gene product. In vitro constructs between the 81-TAg gene, 247 recombinant virus, and ATS-124 xenotropic virus will then be prepared and tested for growth, host range, and oncogenicity. By performing these analyses, we will be able to determine not only the primary structure of the 81-TAg molecule, but also assess its influence on viral phenotype and transformation. Furthermore, by constructing envelope gene expression vectors, we will be able to directly assess the effects of envelope gene expression independent of infectious virus.
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