Inheritance of Susceptibility to Polyoma Virus in Mice2

Abstract

The mode of inheritance of susceptibility to polyoma virus was investigated in neonatal F¹ hybrids and reciprocal backcross progeny of the highly susceptible AKR/J and relatively resistant C57BL/6J strains of mice. Susceptibility to tumorigenesis appeared to be determined by a single autosomal gene with incomplete dominance. Consistently high but apparently submaximal susceptibility of (AKR × C57BL/6)F¹ hybrids was found at both low and high virus dosages. The recessive resistance of the C57BL/6 strain was largely overcome by neonatal infection with polyoma virus in high dosage. High susceptibility of AKR mice to a runting syndrome characterized as a specific acute or subacute manifestation of polyoma disease was recessively inherited. The greatly increased susceptibility to runting of albino compared to black progeny of the F¹ ♀ × AKR ♂ backcross was highly significant at both virus dosages tested. Quantitative genetic analysis of the segregation data showed that susceptibility to runting was effected by interaction of the albino gene (c), or a gene closely linked to it, and another independently segregating recessive gene also carried by the AKR strain. Thus at least 3 independently segregating gene loci must be invoked to account for the over-all evidence of susceptibility. Polyoma tumors frequently developed in the absence of runting, but long-surviving runts always developed tumors. Among other qualifications attached to the genetic analysis given, the incomplete dominance ascribed to the 2 genes governing susceptibility to tumorigenesis and resistance to runting, respectively, might really reflect modifying effects of additional genes. Uniform susceptibility of cell cultures to the multiplication and cytopathic effect of polyoma virus, irrespective of host genotype, revealed that resistance did not depend on the absence of cells subject to continuing infection. Other evidence suggests that early and efficient maturation of the immune-response capacity is a major component of the genetic resistance to malignant infection associated with the C57BL genotype. Increased susceptibility to malignancy (i.e., runting disease and/or tumorigenesis) was positively correlated with reduction in the average latent period for tumor development. The resistance of C57BL mice to tumorigenesis was associated with a strong tendency for tumors to develop only in the salivary glands, whereas AKR mice and their susceptible albino backcross progeny developed multiple tumors with significantly greater frequency.