The Nkx2.1-CreER (or Nkx2.1-CreERT2) knock-in/knock-out allele was designed to both abolish NK2 homeobox 1 (Nkx2-1) gene function and expresses CreER^T2 fusion protein from the Nkx2-1 promoter/enhancer elements. Cre-ERT2 fusion gene activity is inducible; observed following tamoxifen administration. As such, when Nkx2.1-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 Nkx2-1-expressing cells of the offspring.

Heterozygous mice are viable, fertile, and normal in size with no gross physical or behavioral abnormalities reported by the donating investigator (although mice heterozygous from other null mutations of this gene exhibit impaired coordination and high thyroid-stimulating hormone levels). While the donating investigator reports the phenotype of homozygous mice as lethal, they may be expected to have defects similar to mice homozygous for other null mutations of this gene (including profound abnormalities of the ventral forebrain and lungs, a complete lack of thyroids, pituitary gland, and tracheo-esophageal septation, and perinatal death from respiratory failure).

Nkx2.1 mRNA or protein expression from the Nkx2.1-CreER mutant allele was not determined. The donating investigator reports tamoxifen-inducible Cre recombinase activity is specific and efficient; largely recapitulating the endogenous Nkx2-1 expression pattern, with highly efficient inducibility. Tamoxifen-inducible Cre recombinase activity was not tested prior to tamoxifen treatment. Following tamoxifen administration, Cre recombinase activity is observed in Nkx2.1 positive cells; including medial ganglionic eminence (MGE) progenitor cells and preoptic area. 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 (Nkx2-1-CreERT2 images).

If the recombinase activity pattern of this allele is further characterized by the Genetic Resource Science group at The Jackson Laboratory, such findings will be reported on the Mouse Genome Informatics (MGI) Allele Detail entry. This same information may also be found searching the MGI Recombinase Activity and MGI Gene Expression + Recombinase Activity Comparison Matrix.

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.