The keratin 5 gene (Krt5) encodes cytokeratin-5 or K5, a type II cytokeratin specifically expressed in basal epithelial cells (including epidermis, salivary gland and digestive tract). K5 is a biomarker for several different types of cancer (including breast and lung).

The Krt5-CreERT2 knock-in allele has an IRES sequence and a tamoxifen-inducible Cre recombinase (CreER^T2) inserted in the 3' UTR of Krt5. As such, Krt5-CreERT2 mice have both endogenous gene and CreER^T2 expression directed to basal epithelial cells by the endogenous promoter/enhancer elements of the keratin 5 locus. CreER^T2 fusion gene activity is inducible; observed following tamoxifen administration. When Krt5-CreERT2 mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of floxed sequences in the Krt5-expressing cells of the double mutant offspring.


Specifically, tamoxifen-inducible Cre recombinase activity recapitulates the endogenous Krt5 expression pattern. Recombination efficiency is reported to be high in the basal layer of the epidermis, prostate and esophagus, but only 25% in the basal cells of the trachea (which may reflect the lower Krt5 expression in this tissue). The donating investigator did not characterize if Cre recombinase is expressed prior to tamoxifen exposure. Heterozygotes are viable and fertile with no reported abnormalities. To date (May 2016), it has not been attempted to make this strain homozygous.


For example, when Krt5-CreERT2 mice are bred to have a cre-conditional knockout of suppressor of cytokine signals 3 (Socs3^flox; Stock No. 010944) and fluorescent cre-reporter (R26-LSL-EYFP; Stock No. 006148), the resulting triple mutant mice allow tamoxifen-inducible deletion of Socs3 in basal cells and activation of YFP expression as a lineage tracer. Such animals are useful for studying negative feedback regulation / inhibition of the JAK/STAT3 pathway.

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.