| First Author | Brown MA | Year | 2002 |
| Journal | Transgenic Res | Volume | 11 |
| Issue | 5 | Pages | 467-78 |
| PubMed ID | 12437078 | Mgi Jnum | J:79956 |
| Mgi Id | MGI:2429332 | Doi | 10.1023/a:1020348025139 |
| Citation | Brown MA, et al. (2002) Expression of a truncated Brca1 protein delays lactational mammary development in transgenic mice. Transgenic Res 11(5):467-78 |
| abstractText | 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. |
