Mice hemizygous for the Wnt1-CreERT transgene are viable and fertile, with expression of a tamoxifen-inducible Cre recombinase (Cre-ERT) directed by mouse Wnt1 promoter/enhancer elements. CreERT fusion gene activity is inducible; observed following tamoxifen administration. As such, when Wnt1-CreERT 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 Wnt1-expressing cells of the offspring. Depending upon when tamoxifen is administered, Cre recombinase activity may be observed throughout the mesencephalon (midbrain) and rhombomere 1 (~E8.5), or more restricted to the dorsal and ventral midline of the midbrain and a ring around the posterior border of the midbrain (E9.5-12.5), lateral edge of the neural plate (lower rhombic lip) in rhombomere2- rhombomere7, spinal cord and diencephalon, as well as progenitor populations giving rise to migrating neural crest cells and dopaminergic neuron populations (E9.5-12.5). The donating investigator has not determined the phenotype of homozygous mice to date (January 2012).
The Cre-ERT fusion protein consists of Cre recombinase fused to a G521R mutant form of the human estrogen receptor binding domain 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-ERT 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.
