Mouse embryos lacking RXR alpha are resistant to retinoic-acid-induced limb defects.
Mouse embryos lacking RXR alpha are resistant to retinoic-acid-induced limb defects.
复制标题
缺乏 RXR α 的小鼠胚胎能够抵抗视黄酸引起的肢体缺陷。
作者：
H. Sucov;J. Izpisúa;Y. Gańan;R. Evans
胚胎暴露于维生素A代谢物维甲酸（RA）会导致许多发育组织畸形，包括四肢，这是维甲酸作用的模型系统。类风湿关节炎治疗野生型小鼠胚胎导致手指截断和长骨减少。这些作用是由视黄酸和类视黄X受体基因（RARs和RXRs）的产物介导的，它们是配体依赖性转录因子核受体家族的成员。RXR α基因突变纯合的小鼠胚胎在肢体发育中表现正常，尽管这种胚胎在其他组织中会受到表型影响。我们现在描述了在RXR α -/-背景下，对通常由致畸性RA暴露引起的肢体畸形的抵抗力。在100%的野生型胚胎中导致肢体缺陷的RA治疗不能引起RXR α纯合子的畸形，这表明RXR α是肢体致畸过程中的一个组成部分。杂合子胚胎对RA的敏感性为中等，提示RXR α基因剂量在肢体畸形中的重要性。RA诱导基因RAR β 2在野生型和纯合子胚胎中表达相同。类风湿关节炎处理也没有区分野生型和RXR α -/-胚胎在音hedgehog （Shh）和hoxd-12（另外两个与肢体发育有关的基因）的空间表达。然而，在RXR α -/-胚胎中，hoxd-12的定量表达水平升高。这些观察结果表明，外源性RA在小鼠肢体中不适当调节的转录过程需要RXR α来执行，并且特定的致畸过程以及维生素A控制下的特定正常发育过程通过RXR和RAR家族的个体成员发生。
Embryonic exposure to the vitamin A metabolite retinoic acid (RA) causes malformations in numerous developing tissues, including the limbs, which serves as a model system of retinoic acid action. RA treatment of wild-type mouse embryos results in digit truncations and long bone reductions. These effects are mediated by products of the retinoic acid and retinoid X receptor genes (RARs and RXRs), members of the nuclear receptor family of ligand-dependent transcription factors. Mouse embryos homozygous for a mutation in the RXR alpha gene appear normal in limb development, although such embryos are phenotypically affected in other tissues. We now describe resistance to limb malformations normally induced by teratogenic RA exposure in the RXR alpha-/- background. RA treatments that cause limb defects in 100% of wild-type embryos fail to elicit malformations in RXR alpha homozygotes, implicating RXR alpha as a component in the teratogenic process in the limbs. Heterozygous embryos are intermediate in sensitivity to RA, suggesting the importance of RXR alpha gene dosage in limb teratogenesis. Expression of the RA-inducible gene RAR beta 2 was equivalent between wild-type and homozygous embryos after RA treatment. RA treatment also did not distinguish between wild-type and RXR alpha -/- embryos in the spatial expression of sonic hedgehog (Shh) and hoxd-12, two other genes implicated in limb development. However, the quantitative level of hoxd-12 expression was elevated in RXR alpha -/- embryos. These observations indicate that transcriptional processes which are inappropriately regulated in the mouse limb by exogenous RA require RXR alpha for their execution, and that specific teratogenic processes, as well as specific normal developmental processes under vitamin A control, occur through individual members of the RXR and RAR families.
影响因子：
10.5
作者：
SUCOV, HM;DYSON, E;EVANS, RM
通讯作者：
EVANS, RM
视黄酸受体 (RAR) 在发育过程中的功能 (I)。
DOI：
10.1242/dev.120.10.2723
发表时间：
1994
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Lohnes,D;Mark,M;Mendelsohn,C;Dollé,P;Dierich,A;Gorry,P;Gansmuller,A;Chambon,P
通讯作者：
Chambon,P
类视黄醇 X 受体选择性合成类视黄醇的致畸性降低。
影响因子：
5.8
作者：
Jiang,H;Penner,JD;Beard,RL;Chandraratna,RA;Kochhar,DM
通讯作者：
Kochhar,DM