P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity

Drug Metab Dispos. 2018 Nov;46(11):1734-1744. doi: 10.1124/dmd.118.083303. Epub 2018 Aug 9.

Abstract

Preclinical evaluation of drug candidates in experimental animal models is an essential step in drug development. Humanized mouse models have emerged as a promising alternative to traditional animal models. The purpose of this mini-review is to provide a brief survey of currently available mouse models for studying human xenobiotic metabolism. Here, we describe both genetic humanization and human liver chimeric mouse models, focusing on the advantages and limitations while outlining their key features and applications. Although this field of biomedical science is relatively young, these humanized mouse models have the potential to transform preclinical drug testing and eventually lead to a more cost-effective and rapid development of new therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chimera / metabolism*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Disease Models, Animal
  • Humans
  • Inactivation, Metabolic / physiology*
  • Liver / metabolism*
  • Mice
  • Models, Animal
  • Xenobiotics / metabolism*

Substances

  • Xenobiotics
  • Cytochrome P-450 Enzyme System