Gene expression of detoxifying enzymes in AhR and Nrf2 compound null mutant mouse

Shuhei Noda, Nobuhiko Harada, Azumi Hida, Yoshiaki Fujii-Kuriyama, Hozumi Motohashi, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

The arylhydrocarbon receptor (AhR) regulates the expression of cytochrome P450 (CYP)-1 gene family members which catalyze xenobiotic Phase I metabolism, while Nrf2 exerts the concerted regulation of Phase II enzyme genes. We generated AhR and Nrf2 compound null mutant mice to examine the integrated function of AhR- and Nrf2-regulated enzymes in detoxification. Furthermore, we used this mouse model, by administering three different classes of chemical inducers, to examine how xenobiotic metabolism may be influenced in the absence of signals transduced by AhR or Nrf2. The compound mutant mice responded only weakly to AhR ligand or Phase II inducer, while they displayed a clear response to phenobarbital, an inducer of the CYP2B family through another, unrelated transcription factor. Here, we report an initial characterization of the AhR-Nrf2 double mutant mice, which may serve as a simplified bioassay system to evaluate xenobiotic toxicity and metabolic biotransformation of various drugs and environmental chemicals.

Original languageEnglish
Pages (from-to)105-111
Number of pages7
JournalBiochemical and biophysical research communications
Volume303
Issue number1
DOIs
Publication statusPublished - 2003 Mar 28

Keywords

  • 3-Methylchoranthrene
  • Butylated hydroxyanisole
  • Gene knockout mouse
  • Phase I enzymes
  • Phase II enzymes
  • Phenobarbital
  • Xenobiotics

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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