Mice that are homozygous for the targeted mutations are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These mutant mice express CreERT2 from the endogenous Polr2a locus.
When these mice are bred with mice containing a loxP-flanked sequence of interest, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the flanked sequences in Polr2a-expressing tissues
When bred to mice carrying the floxed E4f1tm1.1Llca allele, the double mutant mice (Stock No. 017569) develop epidermal hyperplasia, epidermal cell loss and severe skin ulceration after topical applications of tamoxifen, and may be useful in studies of epidermal stem cells and skin homeostasis.
The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17β-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.
