Identification of a Modifier Locus Affecting Susceptibility to Mammary Tumor Development in Mice

We have been using genetically predisposed mice to identify genes that can modify the risk of mammary tumor development. We have found that a congenic strain of mice that carries as a transgene a retroviral insertion of a LacZ-neoR gene (ROSA26 mice) on chromosome 6, are resistant to Min-induced mammary tumor development. In the ROSA26 mice, the insertion is flanked by about 25 cM of DNA derived from the 129 strain. In order to localize the locus or loci encoding the resistance, we produced mice carrying subsets of the 129 derived DNA form the congenic region. Analysis of six lines indicated that a strong modifier of mammary tumor development mapped within 2 cM of the ROSA26 insertion. This modifier also affects intestinal tumor growth. In addition, prepubertal female and male mice carrying the minimal modifier interval have a significantly smaller extent of mammary gland growth than do age-matched controls. Animals carrying the insertion have slower growth rates than wild-type mice. Finally, we have shown that the effect seen in the ROSA26 mice is due to the insertion and not to linked modifier loci.