A collection of cytochrome P450 humanized and knockout mouse models
Humanized and Knockout Mouse Models for In Vivo Applications
There are profound differences in the pathways that define drug metabolism between rodents and humans. The most important class of drug metabolizing enzymes is constituted by the family of Cytochrome P450 proteins which differ between rodents and humans in their substrate specificity, regulation of expression, and multiplicity. In order to overcome these limitations of traditional rodent animal models we have generated a variety of cytochrome P450 humanized and knockout mouse models which can be used for different in vivo applications.
- Studying human-specific metabolites in vivo
- Examining the in vivo effects of human CYP inhibition
Literature examples: Drug Metab Dispos. 2009 Dec; 37(12):2305-13 and Mol Pharmacol. 2012 Jan; 81(1):63-72.
- Examining the in vivo effects of CYP3A4 induction
Literature example: Mol Pharmacol. 2011 Sep; 80(3):518-28.
- Assessing the impact of gut vs. liver CYP3A4 metabolism on bioavailability
Literature example: J Clin Invest. 2007 Nov; 117(11):3583-92.
- Dissecting the contribution of the Cyp3a family to total bioavailability
- Use of pure inbred genetic background (either C57BL/6 or FVB). This will minimize variance between mice and increase reproducibility of results.
- Corresponding mouse genes are deleted in the humanized models.
- Multiple humanized models available.
- Pre-validation data available.
| Cytochrome P450 Panel | |
|---|---|
| Knockouts | Humanized |
| Cyp1a1/1a2* (contact us) | CYP2C9 |
| Cyp2c | CYP2D6 |
| Cyp2d | CYP3A4/3A7 |
| Cyp3a (7-gene) | Liver CYP3A4 |
| Cyp3a (8-gene) | Gut CYP3A4 |
| Liver & Gut CYP3A4 | |