The Id2-CreERT2 knockin allele was designed to both abolish inhibitor of DNA binding 2 (Id2) gene function and express CreER^T2 fusion protein from the Id2 promoter/enhancer elements. Cre-ERT2 fusion gene activity is inducible and can be observed following tamoxifen administration. As such, when Id2-CreERT2 knockin mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Id2-expressing cells of the offspring.

No mRNA or protein expression from the Id2-CreERT2 allele is observed. The donating investigator reports that homozygous mice are runted with defective lung alveolarization. Other organ systems have not been evaluated. However, Id2-CreERT2 homozygotes may be expected to exhibit the same phenotype as mice homozygous for other null mutations of this gene (including postnatal lethality and defects of the immune system, digestive tract, kidneys, adipose tissue and mammary gland development).Heterozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The donating investigator also reports tamoxifen-inducible Cre recombinase activity recapitulates the endogenous Id2 expression pattern. Following tamoxifen administration, Cre recombinase activity recapitulates the epithelial expression of the endogenous gene (distal tip lung epithelial multipotent precursor cells of the developing lung throughout branching morphogenesis up to embryonic day (E)16.5). Additionally, the Cre recombinase activity in immune cells (during lymphopoiesis, hematopoiesis, or adaptive immune responses) was not directly assessed by the donating investigator. Cre recombinase activity is not observed in lung tissue prior to tamoxifen treatment(other systems not examined).

Of note, the same group designed an identically-targeted Id2-eGFP knockin mouse line to express an enhanced green fluorescent protein (rather than Cre-ERT2 fusion protein) from the Id2 promoter/enhancer elements. That Id2-eGFP knockin mouse line is available as Stock No. 016224.

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.