| Model No. | Nomenclature | Genotype |
|---|---|---|
| 11746 | C57BL/6-Is(19Alb/CYP2C9;Del 19Cyp2c55-Cyp2c70)2Arte | hu/hu |
Humanized Liver CYP2C9 Mouse
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Overview
Nomenclature: C57BL/6-Is(19Alb/CYP2C9;Del 19Cyp2c55-Cyp2c70)2Arte
- This model carries a replacement of fourteen full-length mouse Cyp2c genes (Cyp2c55, 2c65, 2c66, 2c29, 2c38, 2c39, 2c67, 2c68, 2c40, 2c69, 2c37, 2c54, 2c50, 2c70) with an expression cassette encoding human CYP2C9 under control of a liver specific albumin promoter.
- CYP2C9 catalyzes the metabolism of many drugs in clinical use
- May be used as a bioreactor to generate human-specific metabolites, to determine the relevance of CYP2C9 in drug metabolism or for CYP2C9 inhibition studies.
- This model may be used in combination with a Cyp2c knockout model (9177) in order to determine the contribution of CYP2C9-mediated drug metabolism.
Origin
The Humanized Liver CYP2C9 Mouse model was developed by Taconic in collaboration with CXR Biosciences. The model was created by four consecutive rounds of transfection in C57BL/6NTac-derived ES cells. First, mouse exon 1 of Cyp2c55 was replaced with a neomycin cassette containing a loxP and f3 site through gene targeting. Second, a hygromycin cassette with a loxP, lox5171 and frt site was inserted into intron 6 of the Cyp2c70 gene through gene targeting. Third, transfection of the ES cells with cre recombinase resulted in the deletion of the Cyp2c55, 2c65, 2c66, 2c29, 2c38, 2c39, 2c67, 2c68, 2c40, 2c69, 2c37, 2c54, 2c50 and 2c70 genes. Fourth, an albumin-CYP2C9 expression cassette was inserted by cre-mediated recombination into the loxP and lox5171 sites in the mouse Cyp2c locus. The targeted ES cells were injected into BALB/cJBomTac blastocysts and the resultant chimeras were backcrossed to a Flpe deleter strain on C57BL/6J to eliminate selection markers. The colony is maintained by mating homozygotes.
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