Developmental Studies of Brca1 and Brca2 Knock-Out Mice

Developmental Studies of Brca1 and Brca2 Knock-Out Mice 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Mammary Gland and Neoplasia Springer Journals

Developmental Studies of Brca1 and Brca2 Knock-Out Mice

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Publisher
Springer Journals
Copyright
Copyright © 1998 by Plenum Publishing Corporation
Subject
Medicine & Public Health; Cancer Research; Oncology
ISSN
1083-3021
eISSN
1573-7039
D.O.I.
10.1023/A:1018792200700
Publisher site
See Article on Publisher Site

Abstract

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

Journal of Mammary Gland and NeoplasiaSpringer Journals

Published: Sep 28, 2004

References

  • Functions of BRCA1 and BRCA2 genes
    Bertwistle, D.; Ashworth, A.
  • Murine Brca2: sequence, map position, and expression pattern
    Sharan, S. K.; Bradley, A.
  • Cloning, chromosomal mapping and expression pattern of the mouse Brca2 gene
    Connor, F.; Smith, A.; Wooster, R.; Stratton, M.; Dixon, A.; Campbell, E.; Tait, T. M.; Freeman, T.; Ashworth, A.
  • Developmental expression of Brca2 colocalizes with Brca1 and is associated with proliferation and differentiation in multiple tissues
    Rajan, J. V.; Marquis, S. T.; Gardner, H. P.; Chodosh, L. A.
  • Tumor Suppressor gene mutations in mice
    Jacks, T.

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