In humans, the inheritance of mutations in thebreast cancer susceptibility genes BRCA1 and BRCA2increases the risk of developing breast and ovariancancer. To study their biological function and to create animal models for these cancer susceptibilitygenes, several strains of mice mutated in the homologousgenes Brca1 and Brca2 have been generated by genetargeting. Analyses of these “knock-out” mouse mutants have provided invaluableknowledge about the function of these genes. Brca1 andBrca2 null mutants are similar in phenotype: mutationsin both genes result in embryonic lethality and thedeveloping embryos show signs of a cellular proliferationdefect associated with activation of the p53 pathway.The significance of this activation, as well as the roleof these cancer susceptibility genes in DNA damage repair, is discussed.
Journal of Mammary Gland and Neoplasia – Springer Journals
Published: Sep 28, 2004
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