Genetic control by the hr-locus of susceptibility and resistance to leukemia

Abstract

Leukemia was observed in 45 per cent of hairless mice at 8 to 10 months of age and 72 per cent at 18 months. The incidence of leukemia in normal heterozygous mice of the same age is about one per cent at 10 months and increases to 20 per cent at 18 months. Other tumors are rare; two mammary adenocarcinomas occurred in heterozygotes, and an epidermal squamous cell carcinoma was found in a hairless mouse. Murine leukemia virus was isolated from normal and leukemic mice of both genotypes on SWR/J- and C57L/J-METC, but not BALB/cJ-METC. If this virus is responsible for the leukemia in HRS/J mice, the mutant gene (hr) enhances susceptibility and the wild-type allele (+) induces resistance to leukemogenesis, i.e., malignant transformation of reticulo-endothelial tissues occurs rather than inhibition of viral replication as both genotypes harbor virus in high titers. The two types of HRS/J mice, hr/hr and hr/+, are congenic, i.e., they differ only with respect to one allele (hr or +) at the mutant locus. This single gene difference should lend itself to analysis of the interaction of a specific gene and murine leukemia virus.