Mark Manuel, Ghyselinck Norbert B, Chambon Pierre
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut Clinique de la Souris, Centre National de la Recherche Scientifique/INSERM, Université Louis Pasteur de Strasbourg, Collège de France, 67404 Illkirch Cedex, CU de Strasbourg, France.
Annu Rev Pharmacol Toxicol. 2006;46:451-80. doi: 10.1146/annurev.pharmtox.46.120604.141156.
Retinoic acid (RA) is involved in vertebrate morphogenesis, growth, cellular differentiation, and tissue homeostasis. The use of in vitro systems initially led to the identification of nuclear receptor RXR/RAR heterodimers as possible transducers of the RA signal. To unveil the physiological functions of RARs and RXRs, genetic and pharmacological studies have been performed in the mouse. Together, their results demonstrate that (a) RXR/RAR heterodimers in which RXR is either transcriptionally active or silent are involved in the transduction of the RA signal during prenatal development, (b) specific RXRalpha/RAR heterodimers are required at many distinct stages during early embryogenesis and organogenesis, (c) the physiological role of RA and its receptors cannot be extrapolated from teratogenesis studies using retinoids in excess. Additional cell type-restricted and temporally controlled somatic mutagenesis is required to determine the functions of RARs and RXRs during postnatal life.
维甲酸（RA）参与脊椎动物的形态发生、生长、细胞分化和组织稳态。体外系统的使用最初导致核受体RXR/RAR异二聚体被鉴定为RA信号可能的转导因子。为了揭示RARs和RXRs的生理功能，已在小鼠中进行了遗传学和药理学研究。综合起来，它们的结果表明：（a）RXR转录活性或沉默的RXR/RAR异二聚体在产前发育过程中参与RA信号的转导；（b）在早期胚胎发生和器官发生的许多不同阶段需要特定的RXRα/RAR异二聚体；（c）不能从使用过量视黄酸的致畸研究中推断RA及其受体的生理作用。需要额外的细胞类型限制和时间控制的体细胞诱变来确定RARs和RXRs在出生后生活中的功能。
