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

Xi-Ling Jiang1, Frank J Gonzalez, Ai-Ming Yu

  • 1Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, USA.

Drug Metabolism Reviews
|September 22, 2010
PubMed

Insights

Genetically modified mouse models, including knockout and humanized mice, are crucial for understanding drug metabolism and predicting interactions. These models aid in studying drug-metabolizing enzymes, transporters, and receptors in vivo.

Area of Science:

  • Pharmacology and Toxicology
  • Genetics and Genomics

Background:

  • Investigating the in vivo roles of drug-metabolizing enzymes, transporters, and xenobiotic receptors is complex due to gene multiplicity and interactions.
  • Traditional methods face challenges in fully elucidating gene function in drug metabolism and pharmacokinetics.
  • The development of genetically modified mouse models offers a powerful approach to overcome these limitations.

Purpose of the Study:

  • To review successful examples of genetically modified mouse models for drug metabolism research.
  • To discuss the utility of knockout, transgenic, and humanized mice in understanding gene function.
  • To highlight the application of these models in predicting drug-drug interactions and toxicity.

Main Methods:

  • Review of literature on genetically modified mouse models.
  • Analysis of successful applications in studying drug-metabolizing enzymes, transporters, and nuclear receptors.
  • Discussion of knockout (loss-of-function) and transgenic (gain-of-function) mouse models.
  • Consideration of humanized mouse models for interspecies comparisons.

Main Results:

  • Genetically modified mouse models provide invaluable insights into the in vivo function of key drug metabolism components.
  • These models facilitate the study of drug metabolism, transport, and the impact of xenobiotic receptors.
  • Successful examples demonstrate their utility in predicting drug-drug interactions and human toxicity.

Conclusions:

  • Genetically modified mouse models are essential tools for advancing the understanding of drug metabolism and pharmacokinetics.
  • Humanized mice are particularly promising for bridging species differences in drug disposition.
  • Careful interpretation of data is necessary due to potential alterations in gene expression within these models.

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