-edited) The overall goal of this application is to accelerate the progress in breast cancer research by developing a core facility for the propagation and distribution of mice carrying mutations that are believed to be relevant to human breast cancer. Such a core would represent a national resource from which investigators could obtain such mice, as well as tissues or cell lines derived from them, for use in experiments designed to address specific questions concerning the treatment and prevention of breast cancer. The prototype animal with which we propose to initiate this national bank is the BRCA1(+/-) mouse, which we have recently derived at UNC. This mouse carries a targeted mutation that inactivates one allele of the murine analog of the human BRCA1 gene. Mutations in this gene are believed to account for approximately 5 percent of all cases of human breast cancer and 25 percent of cases diagnosed before age 30. This mouse, therefore, serves as a genetic model for the most common form of inherited susceptibility to early onset breast cancer. In addition to making the BRCA1(+/-) mice available to other investigators, we will also undertake the task of introducing the BRCA1 mutation into a number of other established mouse strains. These strains will be chosen so as to provide investigators with better tools for directly addressing the way in which mutations in the BRCA1 gene interact with other genetic factors in the development and progression of breast cancer. These factors would include mutations in other tumor suppressor genes as well as genetic factors affecting immunocompetence. An additional goal of the core facility will be the generation of a mouse line which expresses the cre recombinase primarily in mammary epithelium. Such a mouse line would provide a valuable resource for researchers wishing to study the effects of expression or lack of expression of particular genes on the development or prevention of breast cancer. In addition to providing researchers with new model systems for the study of breast cancer, this facility would also increase the efficiency with which such systems are developed and maintained. Because breeding and maintenance would be carried out at a central facility, the overall cost, as well as the number of animals would be minimized. This would provide an obvious advantage over the present situation, in which the propagation of useful mouse strains often forces researchers to maintain large breeding colonies, even during periods when the strains are not being used for experiments.
| Backlund, M G; Trasti, S L; Backlund, D C et al. (2001) Impact of ionizing radiation and genetic background on mammary tumorigenesis in p53-deficient mice. Cancer Res 61:6577-82 |
| Cressman, V L; Backlund, D C; Hicks, E M et al. (1999) Mammary tumor formation in p53- and BRCA1-deficient mice. Cell Growth Differ 10:1-10 |
| Cressman, V L; Backlund, D C; Avrutskaya, A V et al. (1999) Growth retardation, DNA repair defects, and lack of spermatogenesis in BRCA1-deficient mice. Mol Cell Biol 19:7061-75 |
| Gowen, L C; Avrutskaya, A V; Latour, A M et al. (1998) BRCA1 required for transcription-coupled repair of oxidative DNA damage. Science 281:1009-12 |
