Drug-metabolizing enzyme, transporter, and nuclear receptor genetically modified mouse models

Xi Ling Jiang, Frank J. Gonzalez, Aiming Yu

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27-40
Number of pages14
JournalDrug Metabolism Reviews
Volume43
Issue number1
DOIs
StatePublished - Feb 2011
Externally publishedYes

Fingerprint

Cytoplasmic and Nuclear Receptors
Drug Receptors
Enzymes
Pharmaceutical Preparations
Xenobiotics
Drug-Related Side Effects and Adverse Reactions
Drug Interactions
Genes
Pharmacokinetics
Gene Expression

Keywords

  • cancer
  • drug interaction
  • drug metabolism
  • humanized
  • knockout
  • pharmacokinetics
  • toxicity
  • Transgenic

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Drug-metabolizing enzyme, transporter, and nuclear receptor genetically modified mouse models. / Jiang, Xi Ling; Gonzalez, Frank J.; Yu, Aiming.

In: Drug Metabolism Reviews, Vol. 43, No. 1, 02.2011, p. 27-40.

Research output: Contribution to journalArticle

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