Assessing cytochrome P450 function using genetically engineered mouse models

Sarrah L. Hannon, Xinxin Ding

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The ability to knock out and/or humanize different genes in experimental animals, globally or in cell- and tissue-specific patterns, has revolutionized scientific research in many areas. Genetically engineered mouse models, including knockout models, transgenic models, and humanized models, have played important roles in revealing the in vivo functions of various cytochrome P450 (CYP) enzymes. These functions are very diverse, ranging from the biotransformation of drugs and other xenobiotics, events that often dictate their pharmacokinetic or toxicokinetic properties and the associated therapeutic or adverse actions, to the metabolism of endogenous compounds, such as steroid hormones and other bioactive substances, that may determine susceptibility to many diseases, such as cancer and metabolic diseases. In this review, we provide a comprehensive list of Cyp-knockout, human CYP-transgenic, and CYP-humanized mouse models that target genes in the CYP1–4 gene families, and highlight their utility in assessing the in vivo metabolism, bioactivation, and toxicity of various xenobiotic compounds, including therapeutic agents and chemical carcinogens. We aim to showcase the advantages of utilizing these mouse models for in vivo drug metabolism and toxicology studies, and to encourage and facilitate greater utility of engineered mouse models to further improve our knowledge of the in vivo functions of various P450 enzymes, which is integral to our ability to develop safer and more effective therapeutics and to identify individuals predisposed to adverse drug reactions or environmental diseases.

Original languageEnglish (US)
Title of host publicationPharmacology and Toxicology of Cytochrome P450 - 60th Anniversary
EditorsHiroshi Yamazaki
PublisherAcademic Press Inc.
Pages253-284
Number of pages32
ISBN (Print)9780323911092
DOIs
StatePublished - Jan 2022

Publication series

NameAdvances in Pharmacology
Volume95
ISSN (Print)1054-3589
ISSN (Electronic)1557-8925

Keywords

  • Carcinogenesis
  • Cytochrome P450
  • Drug disposition
  • Drug toxicity
  • Humanized
  • Knockout
  • Mice
  • Transgenic

ASJC Scopus subject areas

  • Pharmacology

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