Homozygous mice die between embryonic day (E)13.5 and birth with defects of heart, kidney, gonads, and multiple other organs. Heterozygous (Wt1^CreERT2/+) mice are viable and fertile. The Wt1^CreERT2 "knock-in" allele both abolishes Wt1 gene function and has expression of the CreER^T2 fusion protein (CreERT2) under control of the Wt1 promoter/enhancer elements. In heart from heterozygous mice, CreERT2 expression is directed to proepicardium and epicardium from E9.5 to E15.5, and is not found in the myocardium. CreERT2 fusion gene activity is inducible; observed following tamoxifen administration. As such, when Wt1^CreERT2 mice are bred with mice containing loxP-flanked sequence, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Wt1-expressing cells of the offspring. The donating investigator reports that Cre activity may be observed prior to tamoxifen exposure only in epicardium of adult mice following myocardial infarction. As Wt1 is expressed in the developing genitourinary system and in the mesothelia overlying most visceral organs, these mutant mice are useful as a tamoxifen-inducible Cre-lox tool for lineage-tracing/marking Wt1-expressing cells for studying cardiomyocytes in the developing heart.

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.