The ER81-CreER (or ER81-CreERT2, Etv1-CreER, Etv1-CreERT2) knock-in allele was designed to both abolish ets variant gene 1 (Etv1) gene function and expresses CreER^T2 fusion protein from the Etv1 promoter/enhancer elements. Cre-ERT2 fusion gene activity is inducible; observed following tamoxifen administration. As such, when ER81-CreERT2 mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Etv1-expressing cells of the offspring.

Heterozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Although mice homozygous for other null mutations of this gene on a similar genetic background exhibit neuromuscular abnormalities, ataxia and premature lethality, the donating investigator reports that ER81-CreER homozygous mice show no gross abnormalities. ER81 mRNA or protein expression from the ER81-CreER mutant allele was not determined. The donating investigator also reports tamoxifen-inducible Cre recombinase activity recapitulates the endogenous Etv1 expression pattern, with moderately efficient inducibility. Tamoxifen-inducible Cre recombinase activity is not observed prior to tamoxifen treatment. Following tamoxifen administration, Cre recombinase activity is observed in ER81 positive cortical neurons (including Layer5 pyramidal neurons). The donating investigators did not examine cre expression in tissues other than brain.

For characterization information, see images at the Allen Institute for Brain Science website (Etv1-CreERT2 images).

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.