The inheritance of susceptibility to the Gross leukemia virus in mice.

ACUTE lymphatic leukemia, originating in the thymus and frequently involving the spleen, lymph nodes and liver, occurs spontaneously in a large percentage of mice of two inbred strains of independent origin: the AK (and its substrain, AKR) and the C58. GROSS ( 195 1,1961 ) has isolated a virus from strain AK leukemic tissues which, when inoculated into mice of the inbred C3Hf/Bi or C57BR strains during the first postnatal days, will induce a high incidence of a similar disease in these normally low-leukemic strains. All four of these inbred mouse strains (AK, C58, C3H and C57BR) possess the complex H-Zk allele in their genetic makeup. The H-2 (Histocompatibility-2) locus controls the major system of antigens responsible for homograft rejection in mice (GORER and MIKULSKA 1959; SNELL 1959; AMOS 1959) and also functions as a blood group determinant. These antigens are found predominantly in tissues with a high content of reticuloendothelial cells (BASCH and STETSON 1962), and during embryonic development their appearance is correlated with the genesis of the lymphatic system ( MOLLER 1963; SCHLESINGER 1964). Because of the presence of the H-2k allele in all of these susceptible strains, it seemed possible that susceptibility to leukemia induction by the Gross virus might be governed by a gene closely linked to or even identical with the H-2 locus or some part of it. The results of a pilot experiment showed a close association, in segregating generations of crosses involving a susceptible strain carrying the H-2k allele and a resistant strain carrying the H-2b allele, between the homozygous H-2k/H-2k phenotype and susceptibility to the virus, and this prompted us to explore the phenomenon in greater detail. A preliminary report, concerning the association between H-2 type and virus susceptibility in these larger experiments, has already appeared ( LILLY, BOYSE and OLD 1964). Further analysis of these results shows that the C3Hf/Bi genome includes at least two unlinked, recessive genes, either one alone capable of conferring susceptibility to the Gross virus. One of these genes either is an allele at the H-2 locus or is closely linked to it, while another segregates independently.