DEVELOPMENTAL STUDIES OF BRCA1 AND BRCA2 KNOCK-OUT MICE

In humans, the inheritance of mutations in the breast cancer susceptib ility genes BRCA1 and BRCA2 increases the risk of developing breast an d ovarian cancer. To study their biological function and to create ani mal models for these cancer susceptibility genes, several strains of m ice mutated in the homologous genes Brca1 and Brca2 have been generate d by gene targeting. Analyses of these ''knock-out'' mouse mutants hav e provided invaluable knowledge about the function of these genes. Brc a1 and Brca2 null mutants are similar in phenotype: mutations in both genes result in embryonic lethality and the developing embryos show si gns of a cellular proliferation defect associated with activation of t he p53 pathway. The significance of this activation, as well as the ro le of these cancer susceptibility genes in DNA damage repair, is discu ssed.