title: Hepatocyte-specific mutation establishes retinoid X receptor alpha as a heterodimeric integrator of multiple physiological processes in the liver.
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 RXRalpha 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 PPARalpha, CARbeta, PXR, LXR, and FXR) is compromised in the absence of RXRalpha. These data demonstrate the presence of a complex circuitry in which RXRalpha 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.
authors.affiliation: Department of Pathology, Harbor-UCLA Medical Center, Torrance, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Wan
authors.forename: D
authors.initials: D
authors.lastname: An
authors.forename: Y
authors.initials: Y
authors.lastname: Cai
authors.forename: J J
authors.initials: JJ
authors.lastname: Repa
authors.forename: T
authors.initials: T
authors.lastname: Hung-Po Chen
authors.forename: M
authors.initials: M
authors.lastname: Flores
authors.forename: C
authors.initials: C
authors.lastname: Postic
authors.forename: M A
authors.initials: MA
authors.lastname: Magnuson
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: K R
authors.initials: KR
authors.lastname: Chien
authors.forename: S
authors.initials: S
authors.lastname: French
authors.forename: D J
authors.initials: DJ
authors.lastname: Mangelsdorf
authors.forename: H M
authors.initials: HM
authors.lastname: Sucov
mesh_terms: D000818:Animals; D006706:Homeostasis / Q000235:genetics; D008099:Liver / Q000502:physiology*; D051379:Mice; D009154:Mutation; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D047488:Retinoid X Receptors; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors