Mice as clinically relevant models for the study of cytochrome P450-dependent metabolism

The cytochrome P450 (CYP) gene superfamily comprises a large group of hemoproteins with diverse functions in steroid, lipid, and xenobiotic metabolism. The human genome is estimated to contain 57 genes that encode functional CYP proteins, a number of which are important for the metabolism of foreign chemicals, including carcinogens and most therapeutic drugs. Given that metabolic interactions are a major source of adverse drug interactions, a comprehensive understanding of CYP function is critically important for the development and safe clinical application of drugs. While some cross-species genetic conservation of CYPs exists, drug metabolism can differ between humans and other mammalian species. The development of humanized mice that replicate many aspects of human drug metabolism has provided invaluable experimental models that circumvent this limitation to a considerable degree. This brief review focuses on the value and limitations of mouse models for the study of drug metabolism in humans.