The Cyp2d Knockout Mouse was developed by Taconic in collaboration with CXR Biosciences. It was generated by crossing a CYP2D6 humanized mouse line with a Flpe deleter mouse. The Humanized CYP2D6 Mouse model 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 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 Cyp2d26 cluster. The Cyp2d Knockout Mouse model was derived from the Humanized CYP2D6 Mouse line through a Flpe-mediated deletion of the human CYP2D6 sequence. The absence of functional Cyp2d proteins was proven experimentally. Taconic received stock in 2009, and the line was embryo transfer derived. The colony is maintained by mating homozygotes.
Scheer N, Kapelyukh Y, Ross J, Beuger V, Stanley LA, Rode A, Wolf CR (2011) Modeling human cytochrome P450 2D6 metabolism and drug-drug interaction by a novel panel of knockout and humanized mouse lines. Mol Pharmacol, October 11, 2011 mol.111.075192, published ahead of print.