Expression of a truncated Brca1 protein delays lactational mammary development in transgenic mice

Transgenic Res. 2002 Oct;11(5):467-78. doi: 10.1023/a:1020348025139.


To address the hypothesis that certain disease-associated mutants of the breast-ovarian cancer susceptibility gene BRCA1 have biological activity in vivo, we have expressed a truncated Brca1 protein (trBrca1) in cell-lines and in the mammary gland of transgenic mice. Immunofluorescent analysis of transfected cell-lines indicates that trBRCA1 is a stable protein and that it is localized in the cell cytoplasm. Functional analysis of these cell-lines indicates that expression of trBRCA1 confers an increased radiosensitivity phenotype on mammary epithelial cells, consistent with abrogation of the BRCA1 pathway. MMTV-trBrca1 transgenic mice from two independent lines displayed a delay in lactational mammary gland development, as demonstrated by altered histological profiles of lobuloalveolar structures. Cellular and molecular analyses indicate that this phenotype results from a defect in differentiation, rather than altered rates of proliferation or apoptosis. The results presented in this paper are consistent with trBrca1 possessing dominant-negative activity and playing an important role in regulating normal mammary development. They may also have implications for germline carriers of BRCA1 mutations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Biomarkers / analysis
  • Blotting, Western
  • DNA Primers / chemistry
  • Epithelial Cells / metabolism*
  • Epithelial Cells / radiation effects
  • Female
  • Fluorescent Antibody Technique
  • Gene Deletion
  • Gene Expression
  • Genetic Vectors
  • In Situ Nick-End Labeling
  • Lactation / physiology*
  • Male
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / physiology*
  • Mammary Glands, Animal / radiation effects
  • Mammary Tumor Virus, Mouse / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Polymerase Chain Reaction
  • Pregnancy
  • Pregnancy, Animal / metabolism*
  • Radiation Tolerance
  • Transfection


  • BRCA1 Protein
  • Biomarkers
  • DNA Primers