TopCreERT2 transgenic mice express a CreER^T2 fusion protein under the control of three copies of a T cell specific transcription factor/lymphoid enhancer-binding factor 1 (TCF/Lef1) response element and a c-fos minimal promoter. Mice hemizygous for the transgene are viable, fertile, and normal in size. Wnt (wingless-related MMTV) family members are required for triggering embryonic axis formation and for proper development. Wnt signaling results in phosphorylation and nuclear localization of β-catenin, a transcriptional co-activator protein, which, together with the TCF/Lef family of transcription factors, induces the transcription of downstream genes. TopCreERT2 transgenic mice contain three copies of nuclear localized TCF/Lef1 DNA binding sites, which provides increased sensitivity to Wnt/β-catenin signaling. Cre-ERT2 fusion gene activity is inducible; observed at high levels following tamoxifen administration. When TopCreERT2 transgenic mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in cells of the double mutant offspring with active Wnt-signaling. Specifically, the TopCreERT2 transgene directs cre expression in the dorsal regions of the otic vesicle of the inner ear. This strain may useful for studying the Wnt signaling pathway.

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.