Kastner P, Mark M, Ghyselinck N, Krezel W, Dupé V, Grondona J M, Chambon P
Institut de Géńetique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP-Collège de France, Illkirch, France.
Development. 1997 Jan;124(2):313-26. doi: 10.1242/dev.124.2.313.
We describe here the analysis of congenital malformations in compound mutant fetuses bearing null alleles in one RXR (alpha, beta or gamma) and one RAR (alpha, beta or gamma) isotype gene. A marked synergy was observed between the effects of mutations in RXR alpha and RARs, as a large number of developmental defects previously found mainly in RAR single and compound mutants were recapitulated in specific RXR alpha/RAR compound mutants. Several malformations were seen only in one type of RXR alpha/RAR mutant combination, whereas others were seen in several types of RXR alpha/RAR double mutants. No synergy was observed between the effects of mutations of either RXR beta or RXR gamma mutations and those of any of the RAR mutations. These genetic data suggest that RXR/RAR heterodimers are the functional units transducing the retinoid signal for a large number of RA-dependent processes, and furthermore, that RXR alpha is the main RXR implicated in the developmental functions of RARs. The significance of these observations is discussed with respect to the problem of functional specificity and redundancy among retinoid receptors in vivo.
我们在此描述了对复合突变胎儿先天性畸形的分析，这些胎儿在一个视黄酸X受体（RXR，α、β或γ）和一个视黄酸受体（RAR，α、β或γ）同种型基因中携带无效等位基因。在RXRα和RARs突变的效应之间观察到显著的协同作用，因为先前主要在RAR单突变体和复合突变体中发现的大量发育缺陷在特定的RXRα/RAR复合突变体中重现。几种畸形仅在一种类型的RXRα/RAR突变体组合中出现，而其他畸形则在几种类型的RXRα/RAR双突变体中出现。在RXRβ或RXRγ突变的效应与任何RAR突变的效应之间未观察到协同作用。这些遗传数据表明，RXR/RAR异二聚体是在大量视黄酸依赖过程中转导视黄酸信号的功能单位，此外，RXRα是参与RARs发育功能的主要RXR。关于体内视黄酸受体之间功能特异性和冗余性的问题，对这些观察结果的意义进行了讨论。
