Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, USA.
Drug Metab Rev. 2011 Feb;43(1):27-40. doi: 10.3109/03602532.2010.512294. Epub 2010 Sep 21.
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.
确定药物代谢和药代动力学中特定酶、转运体或外源性受体的体内意义可能会受到基因多样性和复杂性、表达水平以及涉及的各种成分之间相互作用的阻碍。敲除（功能丧失）和转基因（功能获得）小鼠模型的发展为全面系统地了解基因功能开辟了道路。人们对开发人源化小鼠以克服药物代谢和处置中的种间差异也越来越感兴趣。因此，本综述旨在总结和讨论一些成功的药物代谢酶、转运体和核受体基因修饰小鼠模型的例子。这些基因修饰小鼠模型已被证明是理解药物代谢和转运中药物代谢酶、转运体和外源性受体体内功能以及预测人类潜在药物-药物相互作用和毒性的宝贵模型。然而，人们仍然对从这些基因修饰小鼠模型中获得的数据的解释存在担忧，因为相关基因的表达发生了显著改变。
