Hepatocyte-specific mutation establishes retinoid X receptor α as a heterodimeric integrator of multiple physiological processes in the liver

Yu Jui Yvonne Wan, Dahsing An, Yan Cai, Joyce J. Repa, Tim Hung Po Chen, Monica Flores, Catherine Postic, Mark A. Magnuson, Ju Chen, Kenneth R. Chien, Samuel French, David J. Mangelsdorf, Henry M. Sucov

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

A large number of physiological processes in the adult liver are regulated by nuclear receptors that require heterodimerization with retinoid X receptors (RXRs). In this study, we have used cre-mediated recombination to disrupt the mouse RXRα gene specifically in hepatocytes. Although such mice are viable, molecular and biochemical parameters indicate that every one of the examined metabolic pathways in the liver (mediated by RXR heterodimerization with PPARα, CARβ, PXR, LXR, and FXR) is compromised in the absence of RXRα. These data demonstrate the presence of a complex circuitry in which RXRα is integrated into a number of diverse physiological pathways as a common regulatory component of cholesterol, fatty acid, bile acid, steroid, and xenobiotic metabolism and homeostasis.

Original languageEnglish (US)
Pages (from-to)4436-4444
Number of pages9
JournalMolecular and Cellular Biology
Volume20
Issue number12
DOIs
StatePublished - Jun 2000

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Physiological Phenomena
Retinoid X Receptors
Hepatocytes
Mutation
Liver
Peroxisome Proliferator-Activated Receptors
Xenobiotics
Cytoplasmic and Nuclear Receptors
Metabolic Networks and Pathways
Bile Acids and Salts
Genetic Recombination
Homeostasis
Fatty Acids
Steroids
Cholesterol
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Hepatocyte-specific mutation establishes retinoid X receptor α as a heterodimeric integrator of multiple physiological processes in the liver. / Wan, Yu Jui Yvonne; An, Dahsing; Cai, Yan; Repa, Joyce J.; Chen, Tim Hung Po; Flores, Monica; Postic, Catherine; Magnuson, Mark A.; Chen, Ju; Chien, Kenneth R.; French, Samuel; Mangelsdorf, David J.; Sucov, Henry M.

In: Molecular and Cellular Biology, Vol. 20, No. 12, 06.2000, p. 4436-4444.

Research output: Contribution to journalArticle

Wan, Yu Jui Yvonne ; An, Dahsing ; Cai, Yan ; Repa, Joyce J. ; Chen, Tim Hung Po ; Flores, Monica ; Postic, Catherine ; Magnuson, Mark A. ; Chen, Ju ; Chien, Kenneth R. ; French, Samuel ; Mangelsdorf, David J. ; Sucov, Henry M. / Hepatocyte-specific mutation establishes retinoid X receptor α as a heterodimeric integrator of multiple physiological processes in the liver. In: Molecular and Cellular Biology. 2000 ; Vol. 20, No. 12. pp. 4436-4444.
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AU - Chen, Tim Hung Po

AU - Flores, Monica

AU - Postic, Catherine

AU - Magnuson, Mark A.

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