Developmental studies of Brca1 and Brca2 knock-out mice.
In humans, the inheritance of mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 increases the risk of developing breast and ovarian cancer. To study their biological function and to create animal models for these cancer susceptibility genes, several strains of mice mutated in the homologous genes Brca1 and Brca2 have been generated by gene targeting. Analyses of these "knock-out" mouse mutants have provided invaluable knowledge about the function of these genes. Brca1 and Brca2 null mutants are similar in phenotype: mutations in both genes result in embryonic lethality and the developing embryos show signs of a cellular proliferation defect associated with activation of the p53 pathway. The significance of this activation, as well as the role of these cancer susceptibility genes in DNA damage repair, is discussed.
Hakem
R
R
Amgen Institute and Department of Medical Biophysics, University of Toronto, Ontario, Canada.
de la Pompa
J L
JL
Mak
T W
TW
D000818:Animals; D019313:BRCA1 Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics; D005314:Embryonic and Fetal Development; D005260:Female; D005313:Fetal Death; D018507:Gene Expression Regulation, Developmental; D019398:Genes, BRCA1; D016158:Genes, p53; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors