29. A Mutant Mouse and Breast Cancer
John Schimenti
John C. Schimenti, Biomedical Sciences, and research colleagues’ work with a mutant mouse, Chaos3, that is highly susceptible to mammary tumors, led to finding a potential link between genetic defects in DNA replication and breast cancer. After testing hundreds of mice pedigrees, the researchers identified the Chaos3 line, which has a twentyfold increase in genomic instability, a hallmark for cancer. Most cancers have genomic instability—increased mutations, chromosomal aberrations, and loss of genetic information during DNA replication—by the time they are identified. The researchers showed that genomic instability is leading to these cancers. The mutation occurs in the gene Mcm4, which is essential for DNA replication in both humans and mice. Schimenti and his colleagues found that the DNA codings in Chaos3’s Mcm4 gene were partially impaired, greatly increasing the rate of defective DNA replications and genomic instability. The researchers do not know why the impaired genes in the Chaos3 mice led exclusively to breast cancer. They plan further study on other Mcm genes to find out if they also have a role in cancers.