Mice hemizygous for the INV-CreERT2 transgene are viable and fertile, with expression of CreER^T2 fusion protein directed to the epidermis by the human involucrin (Ivl) promoter. Specifically, the donating investigator reports that the INV-CreERT2 transgene directs reporter gene expression in suprabasal and basal committed cell populations. Cre-ERT2 fusion gene activity is inducible; observed at high levels following tamoxifen administration. When Inv-CreERT2 transgenic mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the INV-expressing cells of the double mutant offspring.

For example, when bred to Gt(ROSA)26Sor^tm1(EYFP)Cos mice (see Stock No. 006148) containing a floxed-STOP cassette followed by a yellow fluorescent protein (YFP), tamoxifen administration results in removal of the STOP cassette and subsequent YFP expression in INV-expressing cells of double mutant offspring. YFP fluorescence is seen in suprabasal cells, and some basal cells, of the interfollicular epidermis of the back skin, tail skin, and the lips. Cells were also labeled in the companion layer of the hair follicle, as well as suprabasal cells of the infundibulum.

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.