The Humanized CYP2D6 Mouse was developed by Taconic in collaboration with CXR Biosciences. It was created by first replacing mouse exon 1 to 4 of Cyp2d26 with a hygromycin cassette containing both loxP and frt sites and subsequently replacing mouse exons 4 and 5 of Cyp2d22 with a genomic human CYP2D6 expression cassette containing additional loxP and frt sites through gene targeting in C57BL/6NTac-derived ES cells. The targeted ES cells were injected into BALB/cJBomTac blastocysts and the resultant chimeras were backcrossed to a Cre deleter strain on C57BL/6J to delete the mouse Cyp2d cluster, while retaining the human CYP2D6 expression cassette. The colony is maintained by mating homozygotes.
Scheer et al. (2012) Modeling Human Cytochrome P450 2D6 Metabolism and Drug-Drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines. Mol Pharmacol. (2012) Jan;81(1):63-72.