GPRC5A (G protein-coupled receptor, family C, group 5, member A) is part of the Retinoic Acid-Inducible G-protein-coupled receptors family and is implicated as an oncogene in some cancers, but a tumor suppressor in others. GPRC5A is highly expressed in lung epithelial cells. These GPRC5A-EGFP-CT-IRES-ERT2-CRE knock-in (KI) mice express enhanced green fluorescent protein (EGFP) and an iCre/ERT2 fusion protein from the endogenous Gprc5a promoter. The EGFP sequence was inserted into the C terminal tail of the GPCR and IRES-iCre/ERT2 into the 3' UTR of the Gprc5a gene. These mice retain endogenous Gprc5a expression.

Homozygous GPRC5A-EGFP-CT-IRES-ERT2-CRE KI mice are viable and fertile with no overt phenotype. The donating laboratory notes that EGFP fluorescence is not observed due to low protein levels of the GPCR. When crossing GPRC5A-EGFP-CT-IRES-ERT2-CRE mice to an Ai9 tdTomato report, resulting progeny demonstrated TdTomato fluorescence in the brain-meninges and lung after tamoxifen exposure. These mice may be useful for lineage-tracing or marking Gprc5a-expressing cells, such as lung epithelial cells.

The iCre-ERT2 fusion protein consists of a codon-improved 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 co-administered. As such, when GPRC5A-EGFP-CT-IRES-ERT2-CRE KI mice are bred with mice containing loxP-flanked sequence of interest, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the floxed sequences in the Gprc5a-expressing cells of the offspring.