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

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 (RXRa, p, and y). They are closely related to each other in their DNAand 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 RXRa. We extend those findings to show that 9-cis RA is also "retinoid X" for mouse RXRa, p, and y. 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.[Key Words: RXRa, p, and 7; vitamin A metabolism; RXR ligands; retinoid receptors in development; nuclear receptor superfamily; 9-cis retinoic acid]

Tissue expression, association analysis between three novel SNPs of the RXRα gene and growth traits in Chinese indigenous cattle

“…The results of real-time PCR analysis revealed that the mRNA of bovine RXR gene was mainly expressed in adipose tissue, heart, liver, spleen, lung, kidney, muscle and testis, which were inconsistent with the previous observations in mouse [8]. Gene expression in what parts of animals was related to its corresponding gene function.…”

“…In expression patterns, the mRNA of RXR gene was highly expressed in liver and kidney tissues in human. In mice, it was also detected abundantly in the tissues of lung, spleen and muscles besides liver and kidney, but it had a low expression level in paranephros, brain, heart, intestine and testis [8]. In swine, Ding et al [9] found the RXR gene abundantly expressed in liver and perirenal adipose tissue.…”

Functional specificity of the two retinoic acid receptor RAR and RXR families in myogenesis

“…RARs bind and are activated by all-trans RA and its 9-cis isomer (Zelent et al, 1989;Allenby et al, 1993), while RXRs bind and are activated by 9-cis RA only Levin et al, 1992;Mangelsdorf et al, 1992). Transcriptional activation through retinoic acid response elements is thought to be mediated by heterodimer formation between RAR and RXR family members, or by homodimer formation of RXRs (Leid et al, 1992a;Zhang et al, 1992;Heery et al, 1993;GigueÁ re, 1994;Glass, 1994).…”

Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta

“…Rxra, Rxrb and Rxrg share a conserved DNA-binding domain (∼95% homology) and C-terminal ligand-binding domain (AF-2, ∼87% homology). In contrast, the sequence of the N-terminal domain (AF-1), which is involved in autonomous ligand-independent transcriptional activation, is divergent across family members 23 . GST pull-down assays showed that the AF-1 domain of Rxrb interacted with CNOT7 whereas the DNA-binding and AF-2 domains did not (Fig.…”