A congenic line of the DDD mouse strain, DDD/1-Mtv-2/Mtv-2: establishment and mammary tumorigenesis.

A single dominant gene on chromosome 18, Mtv-2, controls both the early appearance of mammary tumors and expression of mouse mammary tumor virus (MMTV) in the milk. A congenic DDD mouse strain, DDD/1-Mtv-2/Mtv-2 (DDD-Mtv-2), was developed by introducing this gene from GRS/AJms (GR) into DDD/1 mice by repeating 12 backcrosses and subsequent inbreeding using mammary tumors as a marker for selection. Southern blot analysis of the liver DNA from the resulting congenic mice with EcoRI and MMTV-U3 prove revealed that two DNA fragments corresponding to Mtv-2 were specifically transferred from GR to congenic mice. Detection of MMTV-gp52 antigen in the mammary gland and mammary tumor development in DDDfDDD-Mtv-2 mice demonstrated the production of infectious mature MMTV by Mtv-2 in congenic mice. About 80% of breeding DDD-Mtv-2 females developed mammary tumors in the course of one-year follow-up. The tumor incidence was lower and the tumor age higher than those in GR mice, suggesting less active functioning of the gene on the DDD genetic background. About 70% of these tumors were morphologically classified as pale cell and type P carcinomas peculiar to GR mice. The gene seemed to control the histologic features of mammary tumors. Congenic mice carried an MMTV provirus in an incomplete form on Y chromosome. The DDD-Mtv-2-strain will provide a new model for biological and molecular researches into mouse mammary tumorigenesis.