The Cyp1a2 gene encodes the cytochrome P450, family 1, subfamily a, polypeptide 2 protein expressed in hepatocytes and which accounts for ~12% of the hepatic P450 content in humans. The Cyp1a2-CreER knock-in allele has a tamoxifen-inducible Cre recombinase (CreERT2) inserted into of the 3' UTR of the Cyp1a2 locus. This is designed to have the endogenous Cyp1a2 promoter/enhancer elements directing cre/ERT2 expression primarily in hepatocytes, but not in bile ducts (see below), as well as to retain endogenous Cyp1a2 expression. Specific details are below. CreERT2 fusion gene activity is inducible - observed following tamoxifen administration. As such, when Cyp1a2-CreER mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of floxed sequences in Cyp1a2-expressing cells of the double mutant offspring. The donating investigator reports that Cyp1a2-CreER mice have tamoxifen-inducible Cre recombinase activity that recapitulates the endogenous Cyp1a2 expression pattern - observed mainly in hepatocytes surrounding the central vein in zones 2 and 3. The donating investigator reports no CreERT2 activity (no reporter gene expression) is observed prior to tamoxifen exposure. This knock-in allele is designed to avoid disrupting expression of the endogenous protein; although Cyp1a2 expression from the Cyp1a2-CreER allele has not been evaluated to date (April, 2021). Mice heterozygous for the Cyp1a2-CreER allele are viable and fertile with no reported gross physical or behavioral abnormalities. It has not been attempted to make this strain homozygous to date (April, 2021). 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 (17&beta;-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.

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Cyp1a2-CreER knock-in mice have the endogenous Cyp1a2 promoter/enhancer sequences directing expression of tamoxifen-inducible Cre recombinase. These mice are a Cre-lox tool allowing inducible Cre recombination in Cyp1a2-expressing cells/tissues (including hepatocytes surrounding the central vein in zones 2 and 3), and may be useful in studying hepatocyte proliferation, organization and function.

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