These transgenic mice express a tamoxifen inducible Cre recombinase driven by the mouse Upk2 , uroplakin 2, promoter. When crossed with a strain containing a loxP site flanked sequence of interest, the offspring are useful for generating tamoxifen-induced, Cre-mediated targeted deletions specific to the urothelium. Tamoxifen administration induces Cre recombination in the urothelium Upk2 expressing cells of bladder, ureter, and the renal pelvis of the kidney. No inducible Cre recombinase activity was detected in intestine, lung, heart, liver, spleen, testis, prostate, ovary, uterus, skin, thymus, cerebellum, cerebrum, or stomach. Homozygous mutant mice are viable and fertile.
The Cre-ERT2 fusion protein (Cre-ERT2) consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor; which does not bind its natural ligand (17?-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.
