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Related Experiment Videos

MMTV-trBrca1 mice display strain-dependent abnormalities in vaginal development.

Kaylene J Simpson1, Mas R Wati, Andrew J Deans

  • 1Department of Biochemistry and Molecular Biology, University of Melbourne, Victoria, Australia.

The International Journal of Developmental Biology
|October 8, 2004
PubMed
Summary

The breast cancer gene Brca1 (BRCA1) plays a role in normal development. Disrupting BRCA1 in mice inhibited vaginal remodeling and increased resistance to apoptosis in mammary cells.

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Area of Science:

  • Genetics
  • Developmental Biology
  • Cancer Biology

Background:

  • The breast cancer susceptibility gene Brca1 encodes a multi-functional protein involved in genome maintenance.
  • BRCA1's role in DNA damage response pathways, including apoptosis, is established.
  • Apoptosis is crucial for normal physiological processes, including development.

Purpose of the Study:

  • To investigate the role of BRCA1 in normal developmental processes mediated by apoptosis.
  • To determine if disruption of BRCA1 affects vaginal entrance remodeling in mice.
  • To explore the impact of BRCA1 disruption on apoptosis resistance in epithelial cells.

Main Methods:

  • Generation of mice expressing a dominant-negative Brca1 transgene on a BALB/c background.

Related Experiment Videos

  • Analysis of vaginal entrance remodeling in Brca1 transgene-expressing mice, with and without a p53 +/- genotype.
  • In vitro studies assessing the resistance of mammary epithelial cells with BRCA1 transgene expression to ionizing radiation-induced cell killing.

    • Main Results:

    • Dominant-negative Brca1 transgene expression inhibited vaginal entrance remodeling in mice.
    • The incidence of inhibited vaginal remodeling was increased in mice with a p53 +/- genotype.
    • Mammary epithelial cells expressing the Brca1 transgene exhibited resistance to ionizing radiation-induced cell killing in vitro.

    Conclusions:

    • BRCA1 disruption inhibits apoptosis-mediated normal development, specifically vaginal entrance remodeling.
    • BRCA1 disruption confers resistance to apoptosis in normal epithelial cells.
    • This study implicates BRCA1 in an apoptosis-mediated normal developmental process for the first time.