A Congenic Line of the DDD Mouse Strain, DDD/1‐Mtv‐2/Mtv‐2: Establishment and Mammary Tumorigenesis

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Abstract
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 probe 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.