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

First Author  Mangelsdorf DJ Year  1992
Journal  Genes Dev Volume  6
Issue  3 Pages  329-44
PubMed ID  1312497 Mgi Jnum  J:2326
Mgi Id  MGI:50850 Doi  10.1101/gad.6.3.329
Citation  Mangelsdorf DJ, et al. (1992) Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev 6(3):329-44
abstractText  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 (RXR alpha, beta, and gamma). 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 RXR alpha. We extend those findings to show that 9-cis RA is also retinoid X for mouse RXR alpha, beta, and gamma. 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.
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