1992 | David J. Mangelsdorf, Uwe Borgmeyer, Richard A. Heyman, J. Yang Zhou, Estelita S. Ong, Anthony E. Oro, Akira Kakizuka, and Ronald M. Evans
This study characterizes three retinoid X receptor (RXR) genes in mice: RXRα, RXRβ, and RXRγ. These genes encode distinct receptors that are closely related in their DNA- and ligand-binding domains but differ significantly from the retinoic acid receptor (RAR) subfamily in structure and ligand specificity. The study shows that 9-cis retinoic acid (9-cis RA) is a high-affinity ligand for all three RXR subtypes, making it a "retinoid X" for mouse RXRα, β, and γ. Unlike all-trans RA, 9-cis RA is more potent in activating RXR-mediated transactivation. Northern blot and in situ hybridization analyses reveal broad expression patterns for RXRs, with unique expression profiles that partially overlap with RARs. The RXR family is proposed to play critical roles in various developmental processes, including embryo implantation, organogenesis, and central nervous system differentiation, as well as in adult physiology. The study also highlights the importance of RXR in vitamin A metabolism and its potential role in retinoid signaling pathways. The discovery of three RXR subtypes and their specific ligands, along with their expression patterns, defines a complex regulatory system in which RXRs may have widespread roles in development and adult physiology.This study characterizes three retinoid X receptor (RXR) genes in mice: RXRα, RXRβ, and RXRγ. These genes encode distinct receptors that are closely related in their DNA- and ligand-binding domains but differ significantly from the retinoic acid receptor (RAR) subfamily in structure and ligand specificity. The study shows that 9-cis retinoic acid (9-cis RA) is a high-affinity ligand for all three RXR subtypes, making it a "retinoid X" for mouse RXRα, β, and γ. Unlike all-trans RA, 9-cis RA is more potent in activating RXR-mediated transactivation. Northern blot and in situ hybridization analyses reveal broad expression patterns for RXRs, with unique expression profiles that partially overlap with RARs. The RXR family is proposed to play critical roles in various developmental processes, including embryo implantation, organogenesis, and central nervous system differentiation, as well as in adult physiology. The study also highlights the importance of RXR in vitamin A metabolism and its potential role in retinoid signaling pathways. The discovery of three RXR subtypes and their specific ligands, along with their expression patterns, defines a complex regulatory system in which RXRs may have widespread roles in development and adult physiology.