The Calb2-CreERT2 (CR-CreER or CR-CreERT2) knock-in allele was designed to both abolish Calb2 (calbindin 2; also called calretinin or CR) gene function and expresses CreER^T2 fusion protein from the Calb2 promoter/enhancer elements. Cre-ERT2 fusion gene activity is inducible; observed following tamoxifen administration. As such, when CR-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 CR-expressing cells of the offspring.

Heterozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The donating investigator reports that the phenotype of CR-CreER homozygous mice has not been assessed. However, CR-CreER homozygotes may be expected to exhibit the same phenotype as mice homozygous for other null mutations of this gene on a similar genetic background (impaired motor coordination, abnormal nervous system electrophysiology, and impaired long-term potentiation induction in dentate gyrus). Calretinin mRNA or protein expression from the CR-CreER mutant allele was not determined. The donating investigator also reports tamoxifen-inducible Cre recombinase activity recapitulates the endogenous calretinin expression pattern, but with moderate efficiency of induction. In olfactory bulb, the induction efficiency is higher. Tamoxifen-inducible Cre recombinase activity is not observed prior to tamoxifen treatment. Following tamoxifen administration, Cre recombinase activity is observed in calretinin positive interneurons in the brain. 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 (Calb2-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.