Mammary-specific targeting of the murine BRCA2 breast cancer susceptibility gene in mice

Autor: Kimberly A. McAllister, N K Collins, K-U Wagner, Roger W. Wiseman, Edward M. Eddy, G Goulding, Jason Malphurs, Toni Ward, L M Bennett, Barbara J. Davis
Rok vydání: 2000
Předmět:
Zdroj: Breast Cancer Research. 2
ISSN: 1465-542X
DOI: 10.1186/bcr150
Popis: BRCA2 hereditary gene mutations confer a profound predisposition to breast cancer in women. We have generated mice carrying a Cre-loxP conditional Erca2 mutated allele by flanking exon 27 with loxP sites and we predict that this will disrupt basic functions of Brca2 in DNA repair. The mammary- specific removal of Brca2 exon 27 by Cre-mediated recombination in vivo was performed by crossing the homozygous floxed Brca2 mice with MMTV-Cre transgenic mice. The effect of-this mutation on the formation of mammary gland tumors and alterations in mammary gland morphogenesis is currently being examined for both untreated and radiation-treated animals. Mice with a homozygous germline deletion of Brca2 exon 27 have also been created by transiently electroporating embryonic stem cells carrying the floxed Brca2 allele with a Cre-expression plasmid. These studies have generated the first completely viable germline homozygous Erca2 knockout mice. Female mice with this homozygous Brce2 disruption display an inhibition of ductal morphogenesis in the mammary gland by six months of age, which may be an early biological marker for cancer susceptibility. Parallel studies using these two distinct animal models for Brca2 inactivation should provide valuable insights into the functional role of Brca2 in the breast ahd throughout the body.
Databáze: OpenAIRE