Genetic control of sensitivity to Moloney-virus-induced leukemias in mice. I. Demonstration of multigenic control.

The appearance of hematopoietic malignancies and the level of viremia were studied in mice of different inbred strains and their F1 or F2 hybrids inoculated with the Moloney leukemia virus (MLV). The viremia was regularly measured in individual mice by radioimmunoassay of the major internal virion component p30. A complex genetic control was found. (1) The level of circulating virus was controlled by at least two genes. An H-2 linked gene, tentatively called Rmv-1, displayed a dominant sensitivity. Alleles for resistance existed in H2b and H-2r haplotypes and alleles for sensitivity in H-2a, H-2d and H-2f. Another gene with dominant resistance mapped outside the H-2 complex and probably interacted with Rmv-1. (2) A good correlation existed between viremia and the appearance of leukemias, the most viremic strains being also the most leukemic. (3) Nevertheless, additional genes which were not involved in the viremia control could be determinant in the induction of malignancies. One of them with a resistant allele in DBA/2 mice seemed to inhibit the appearance of leukemia despite a high level of viremia. Another gene controlled the spleen involvement resulting in generalized leukemias in sensitive lines contrasting with mainly thymus-localized tumors in resistant animals.