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This targeted mutation strain carries a replacement of the nine functional mouse Cyp2d genes (Cyp2d22, Cyp2d11, Cyp2d10, Cyp2d9, Cyp2d12, Cyp2d34, Cyp2d13, Cyp2d40, Cyp2d26) with approximately 13 kb of genomic human DNA comprising CYP2D6.
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CYP2D6 catalyzes the metabolism of more than 20% of drugs in clinical use and is highly polymorphic in humans.
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May be used as a bioreactor to generate human-specific metabolites, to determine the relevance of CYP2D6 in drug metabolism or for CYP2D6 inhibition studies.
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May be used with 9178, which is knocked out for the mouse Cyp2d cluster, to predict the differences in response of human poor and extensive CYP2D6 metabolisers.
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.
Genetic Background:
C57BL/6 Background
Origin:
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.
Color:
Black
Species:
Mouse
Initial Publication:
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.
