Mutant Mouse: Brca1 (Breast cancer1)
Knockout of the BRCA1 (Breast Cancer 1) gene impairs DNA damage repair resulting in embryonic death.
Germ-line mutations of the nuclear protein BRCA1 are responsible for increased susceptibility to familial breast and ovarian cancers. Targeted mutation of exon 11 of mouse BRCA1 results in embryonic lethality early in embryogenesis. Embryos containing a Brca1 null mutation are hypersensitive to gamma irradiation and exhibit structural DNA damage, supporting a role for BRCA1 in DNA damage repair. The chromosomal abnormalities were more massive in a p53 null background, suggesting that the loss of p53 acting at cell cycle checkpoints allows cells with damaged DNA to accumulate. The additional mutations may account for the tumorigenesis associated with Brca1 mutations in humans.