Transgenic mice exhibiting inducible and spontaneous Cre activities driven by a bovine keratin 5 promoter that can be used for the conditional analysis of basal epithelial cells in multiple organs

In this study, we have generated two distinct transgenic mouse lines expressing CreERT, which show 4-hydroxytamoxifen (4-OHT)-inducible and spontaneous (4-OHT-independent) Cre activities, referred to Tg(BK5-CreERT)I and Tg(BK5-CreERT)S, respectively. The transgenic construct is driven by the bovine Keratin 5 promoter, which is active in the basal epithelial lineage of stratified and pseudo-stratified epithelium across multiple organs. Despite the difference in 4-OHT dependency, the Tg(BK5-CreERT)I and Tg(BK5-CreERT)S mouse lines shared similar Cre-mediated recombination among various organs, except for unique mammary epithelial Cre activity in Tg(BK5-CreERT)S females.These two new transgenic mouse lines for the analysis of basal epithelial function and for the genetic modification have been created allowing the identification of these cell lineages and analysis of their differentiation during embryogenesis, during perinatal development and in adult mice.Gene targeting provides a powerful tool to address gene function by the manipulation of the mouse genome through homologous recombination in embryonic stem (ES) cells (reviewed in [1]). However, germ-line genetic modification often causes lethality or numerous effects that interfere with the analysis of specific biological phenotypes. Conditional gene targeting using the Cre/loxP-mediated recombination system (reviewed in [1,2]) offers an alternative approach for the dissection of gene function. Cre recombinase expression can be regulated by tissue or cell-type specific promoters in transgenic mouse lines. Thus, Cre can recognize loxP sites to catalyze site-specific recombination in a tissue/cell specific manner. In addition to tissue/cell specific regulation of Cre expression, temporal control of Cre recombinase activity in transgenic mice has been demonstrated utilizing Cre recombinase fused with the mutated hormone-binding domain of the estrogen receptor (ERT); this can be activated by the synthetic estrogen analo