Separation of high mammary tumor incidence from high hepatoma incidence in backcross mice during segregation of the viable yellow gene.

Abstract

AbstractMammary tumorigenesis in strain C3H‐vyfB female mice (approximately 90% incidence) is not due to exogenous mouse mammary tumor virus (MMTV) but to genetic factors transmitted by either parent. Prominent among these genetic factors is the viable yellow (Avy) gene which may increase either the virulence of the endogenous MMTV provirus (Mtv‐l) by promoting expression or the susceptibility of the mammary tissue to tumorigenesis by endogenous MMTV. Crosses were made between the viable yellow strain, C3H‐AvyfB/He(AvyAay) and C3H/Sm (AA) to give heterozygous (AvyA) F1 yellow hybrids from which yellow (Avy) and agouti (AA) back‐cross progeny were produced by mating with C3H/Sm males. AvyA backcross females were expected to have at least twice as many mammary tumors as the AA back‐cross females if the Avy gene were solely responsible for the high incidence of mammary tumors in C3H‐AvyfB since mammary tumor incidence is 90% in AvyfB and 40% in (AA)C3HfB. Alternatively, if the high tumor incidence in C3H‐AvyB were due to a more active endogenous MMTV (Mtv‐l), then a much smaller difference in the mammary tumor incidence of AvyA versus AA backcross females would be expected. The more reactive endogenous MMTV would occur equally between yellow and agouti females, since the C3H Mtv‐l gene is present on a separate chromosome from the Avygene. Unexpectedly, the F1 hybrid females (AvyA) developed mammary tumors at a relatively low rate (28.9%) although hepatoma incidence remained high (89.5%). Both yellow (AvyA) and agouti (AA) backcross females showed an even greater reduction in mammary tumor incidence, 7.9% and 3.8% respectively. In contrast, the high rate of spontaneous hepatoma development segregated with the Avy gene since 86‐5% of the yellow (AvyA) backcross females development hepatomas by 19 months of age, while only 25% of the agouti (AA) backcross females had liver tumors at 24.4 months. The reduction of mammary tumor incidence in (C3H‐AvyfB × C3H/Sm)F1 hybrids was unexpected since earlier studies had shown that reciprocal F1, hybrids between strains BALB/c and C3H‐AvyfB continued to show a 90% mammary tumor incidence. The present result is consistent with the possibility that strain C3H/Sm possesses a heritable factor(s) which attenuates the ability of endogenous MMTV to malignantly transform mammary epithelium.