Characterization of three RXR genes that mediate the action of 9-cis retinoic acid

David J. Mangelsdorf, Uwe Borgmeyer, Richard A. Heyman, J. Yang Zhou, Estelita S. Ong, Anthony E. Oro, Akira Kakizuka, Ronald M. Evans

Research output: Contribution to journalArticle

1006 Scopus citations

Abstract

An understanding of the differences and similarities of the retinoid X receptor (RXR) and retinoic acid receptor (RAR) systems requires knowledge of the diversity of their family members, their patterns of expression, and their pharmacological response to ligands. In this paper we report the isolation of a family of mouse RXR genes encoding three distinct receptors (RXRα, β, and γ). They are closely related to each other in their DNA- and ligand-binding domains but are quite divergent from the RAR subfamily in both structure and ligand specificity. Recently, we demonstrated that all-trans retinoic acid (RA) serves as a "pro-hormone" to the isomer 9-cis RA, which is a high-affinity ligand for the human RXRα. We extend those findings to show that 9-cis RA is also "retinoid X" for mouse RXRα, β, and γ. Trans-activation analyses show that although all three RXRs respond to a variety of endogenous retinoids, 9-cis RA is their most potent ligand and is up to 40-fold more active than all-trans RA. Northern blot and in situ hybridization analyses define a broad spectrum of expression for the RXRs, which display unique patterns and only partially overlap themselves and the RARs. This study suggests that the RXR family plays critical roles in diverse aspects of development, from embryo implantation to organogenesis and central nervous system differentiation, as well as in adult physiology.

Original languageEnglish (US)
Pages (from-to)329-344
Number of pages16
JournalGenes and Development
Volume6
Issue number3
StatePublished - 1992

    Fingerprint

Keywords

  • 9-cis retinoic acid
  • Nuclear receptor superfamily
  • Retinoid receptors in development
  • RXR ligands
  • RXRα, β, and γ
  • Vitamin A metabolism

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Mangelsdorf, D. J., Borgmeyer, U., Heyman, R. A., Yang Zhou, J., Ong, E. S., Oro, A. E., Kakizuka, A., & Evans, R. M. (1992). Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes and Development, 6(3), 329-344.