CRE-MEDIATED GENE DELETION IN THE MAMMARY-GLAND

To delete genes specifically from mammary tissue using the Cre-lox sys tem,we have established transgenic mice expressing Cre recombinase und er control of the WAP gene promoter and the MMTV LTR, Cre activity in these mice was evaluated by three criteria. First, the tissue distribu tion of Cre mRNA was analyzed, Second, an adenovirus carrying a report er gene was used to determine expression at the level of single cells. Third, tissue specificity of Cre activity was determined in a mouse s train carrying a reporter gene, In adult MMTV-Cre mice expression of t he transgene was confined to striated ductal cells of the salivary gla nd and mammary epithelial cells in virgin and lactating mice. Expressi on; of WAP-Cre was only detected in alveolar epithelial cells of mamma ry tissue during lactation, Analysis of transgenic mice carrying both the MMTV-Cre and the reporter transgenes revealed recombination in eve ry tissue, In contrast, recombination mediated by Cre under control of the WAP gene promoter was largely restricted to the mammary gland but occasionally observed in the brain. These results show that transgeni c mice with WAP-Cre but not MMTV-Cre can be used as a powerful tool to study gene function in development and tumorigenesis in the mammary g land.