Humanized transgenic mouse models for drug metabolism and pharmacokinetic research

Hong Wu Shen, Xi Ling Jiang, Frank J. Gonzalez, Aiming Yu

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Extrapolation of the metabolic, pharmacokinetic and toxicological data obtained from animals to humans is not always straightforward, given the remarkable species difference in drug metabolism that is due in large part to the differences in drugmetabolizing enzymes between animals and humans. Furthermore, genetic variations in drug-metabolizing enzymes may significantly alter pharmacokinetics, drug efficacy and safety. Thus, humanized transgenic mouse lines, in which the human drug-metabolizing enzymes are expressed in mouse tissues in the presence or absence of mouse orthologues, have been developed to address such challenges. These humanized transgenic mice are valuable animal models in understanding the significance of specific human drug-metabolizing enzymes in drug clearance and pharmacokinetics, as well as in predicting potential drug-drug interactions and chemical toxicity in humans. This review, therefore, aims to summarize the development and application of some humanized transgenic mouse models expressing human drug-metabolizing enzymes. The limitations of these genetically modified mouse models are also discussed.

Original languageEnglish (US)
Pages (from-to)997-1006
Number of pages10
JournalCurrent Drug Metabolism
Volume12
Issue number10
DOIs
StatePublished - Dec 2011
Externally publishedYes

Fingerprint

Pharmacokinetics
Metabolism
Transgenic Mice
Research
Pharmaceutical Preparations
Enzymes
Animals
Drug interactions
Drug Interactions
Extrapolation
Toxicology
Toxicity
Animal Models
Tissue
Safety

Keywords

  • Cancer
  • Drug interaction
  • Drug metabolism
  • Humanized
  • Mouse model
  • Pharmacokinetics
  • Toxicity
  • Transgenic

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Biochemistry

Cite this

Humanized transgenic mouse models for drug metabolism and pharmacokinetic research. / Shen, Hong Wu; Jiang, Xi Ling; Gonzalez, Frank J.; Yu, Aiming.

In: Current Drug Metabolism, Vol. 12, No. 10, 12.2011, p. 997-1006.

Research output: Contribution to journalArticle

Shen, Hong Wu ; Jiang, Xi Ling ; Gonzalez, Frank J. ; Yu, Aiming. / Humanized transgenic mouse models for drug metabolism and pharmacokinetic research. In: Current Drug Metabolism. 2011 ; Vol. 12, No. 10. pp. 997-1006.
@article{c623222914f542ff8bfef026b6ee5d1e,
title = "Humanized transgenic mouse models for drug metabolism and pharmacokinetic research",
abstract = "Extrapolation of the metabolic, pharmacokinetic and toxicological data obtained from animals to humans is not always straightforward, given the remarkable species difference in drug metabolism that is due in large part to the differences in drugmetabolizing enzymes between animals and humans. Furthermore, genetic variations in drug-metabolizing enzymes may significantly alter pharmacokinetics, drug efficacy and safety. Thus, humanized transgenic mouse lines, in which the human drug-metabolizing enzymes are expressed in mouse tissues in the presence or absence of mouse orthologues, have been developed to address such challenges. These humanized transgenic mice are valuable animal models in understanding the significance of specific human drug-metabolizing enzymes in drug clearance and pharmacokinetics, as well as in predicting potential drug-drug interactions and chemical toxicity in humans. This review, therefore, aims to summarize the development and application of some humanized transgenic mouse models expressing human drug-metabolizing enzymes. The limitations of these genetically modified mouse models are also discussed.",
keywords = "Cancer, Drug interaction, Drug metabolism, Humanized, Mouse model, Pharmacokinetics, Toxicity, Transgenic",
author = "Shen, {Hong Wu} and Jiang, {Xi Ling} and Gonzalez, {Frank J.} and Aiming Yu",
year = "2011",
month = "12",
doi = "10.2174/138920011798062265",
language = "English (US)",
volume = "12",
pages = "997--1006",
journal = "Current Drug Metabolism",
issn = "1389-2002",
publisher = "Bentham Science Publishers B.V.",
number = "10",

}

TY - JOUR

T1 - Humanized transgenic mouse models for drug metabolism and pharmacokinetic research

AU - Shen, Hong Wu

AU - Jiang, Xi Ling

AU - Gonzalez, Frank J.

AU - Yu, Aiming

PY - 2011/12

Y1 - 2011/12

N2 - Extrapolation of the metabolic, pharmacokinetic and toxicological data obtained from animals to humans is not always straightforward, given the remarkable species difference in drug metabolism that is due in large part to the differences in drugmetabolizing enzymes between animals and humans. Furthermore, genetic variations in drug-metabolizing enzymes may significantly alter pharmacokinetics, drug efficacy and safety. Thus, humanized transgenic mouse lines, in which the human drug-metabolizing enzymes are expressed in mouse tissues in the presence or absence of mouse orthologues, have been developed to address such challenges. These humanized transgenic mice are valuable animal models in understanding the significance of specific human drug-metabolizing enzymes in drug clearance and pharmacokinetics, as well as in predicting potential drug-drug interactions and chemical toxicity in humans. This review, therefore, aims to summarize the development and application of some humanized transgenic mouse models expressing human drug-metabolizing enzymes. The limitations of these genetically modified mouse models are also discussed.

AB - Extrapolation of the metabolic, pharmacokinetic and toxicological data obtained from animals to humans is not always straightforward, given the remarkable species difference in drug metabolism that is due in large part to the differences in drugmetabolizing enzymes between animals and humans. Furthermore, genetic variations in drug-metabolizing enzymes may significantly alter pharmacokinetics, drug efficacy and safety. Thus, humanized transgenic mouse lines, in which the human drug-metabolizing enzymes are expressed in mouse tissues in the presence or absence of mouse orthologues, have been developed to address such challenges. These humanized transgenic mice are valuable animal models in understanding the significance of specific human drug-metabolizing enzymes in drug clearance and pharmacokinetics, as well as in predicting potential drug-drug interactions and chemical toxicity in humans. This review, therefore, aims to summarize the development and application of some humanized transgenic mouse models expressing human drug-metabolizing enzymes. The limitations of these genetically modified mouse models are also discussed.

KW - Cancer

KW - Drug interaction

KW - Drug metabolism

KW - Humanized

KW - Mouse model

KW - Pharmacokinetics

KW - Toxicity

KW - Transgenic

UR - http://www.scopus.com/inward/record.url?scp=82255169463&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82255169463&partnerID=8YFLogxK

U2 - 10.2174/138920011798062265

DO - 10.2174/138920011798062265

M3 - Article

C2 - 22023319

AN - SCOPUS:82255169463

VL - 12

SP - 997

EP - 1006

JO - Current Drug Metabolism

JF - Current Drug Metabolism

SN - 1389-2002

IS - 10

ER -