Characterization of a murine Ahr null allele: Involvement of the Ah receptor in hepatic growth and development

Jennifer V. Schmidt, Gloria Huei Ting Su, Janardan K. Reddy, M. Celeste Simon, Christopher A. Bradfield*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

705 Scopus citations

Abstract

The Ah receptor (AHR) is a ligand-activated transcription factor that mediates a pleiotropic response to environmental contaminants such as benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. In an effort to gain insight into the physiological role of the AHR and to develop models useful in risk assessment, gene targeting was used to inactivate the murine Ahr gene by homologous recombination. Ahr(-/-) mice are viable and fertile but show a spectrum of hepatic defects thai indicate a role for the AHR in normal liver growth and development. The Ahr(-/-) phenotype is most severe between 0-3 weeks of age and involves slowed early growth and hepatic defects, including reduced liver weight, transient microvesicular fatty metamorphosis, prolonged extramedullary hematopoiesis, and portal hypercellularity with thickening and fibrosis.

Original languageEnglish (US)
Pages (from-to)6731-6736
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number13
DOIs
StatePublished - Jun 25 1996

Keywords

  • 2,3,7,8-tetrachlorodibenzo-p-dioxin
  • dioxin
  • gene targeting
  • liver

ASJC Scopus subject areas

  • General

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