Drug-metabolizing enzyme, transporter, and nuclear receptor genetically modified mouse models.
Determining the in vivo significance of a specific enzyme, transporter, or xenobiotic receptor in drug metabolism and pharmacokinetics may be hampered by gene multiplicity and complexity, levels of expression, and interaction between various components involved. The development of knockout (loss-of-function) and transgenic (gain-of-function) mouse models opens the door to the improved understanding of gene function in a whole-body system. There is also growing interest in the development of humanized mice to overcome species differences in drug metabolism and disposition. This review, therefore, aims to summarize and discuss some successful examples of drug-metabolizing enzyme, transporter, and nuclear-receptor genetically modified mouse models. These genetically modified mouse models have been proven as invaluable models for understanding in vivo function of drug-metabolizing enzymes, transporters, and xenobiotic receptors in drug metabolism and transport, as well as predicting potential drug-drug interaction and toxicity in humans. Nevertheless, concerns remain about interpretation of data obtained from such genetically modified mouse models, in which the expression of related genes is altered significantly.
Jiang
Xi-Ling
XL
Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, USA.
Gonzalez
Frank J
FJ
Yu
Ai-Ming
AM
D000818:Animals; D030801:Animals, Genetically Modified; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D055808:Drug Discovery; D006801:Humans; D008658:Inactivation, Metabolic; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015262:Xenobiotics / Q000493:pharmacokinetics*
D026901:Membrane Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System