RXR-ALPHA MUTANT MICE ESTABLISH A GENETIC-BASIS FOR VITAMIN-A SIGNALING IN HEART MORPHOGENESIS
RXR-ALPHA MUTANT MICE ESTABLISH A GENETIC-BASIS FOR VITAMIN-A SIGNALING IN HEART MORPHOGENESIS
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DOI：
10.1101/gad.8.9.1007
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发表时间：
1994-05-01
影响因子：
10.5
通讯作者：
EVANS, RM
中科院分区：
文献类型：
--
作者：
SUCOV, HM;DYSON, E;EVANS, RM
我们已经在小鼠生殖系中的RXR α基因中建立了一个靶向功能缺失突变，当繁殖至纯合性时，该突变导致E13.5和E16.5之间的胚胎致死。导致死亡的主要缺陷是心室腔发育不全，表现为心室壁明显变薄，同时伴有心室间隔缺陷。这种表型与胚胎维生素A缺乏的影响的子集相同，因此，将RXR α确立为心脏形态发生中维生素A信号通路的遗传组分。心脏流出道和相关的血管，这是由神经嵴的衍生物，这也是敏感的维生素A缺乏症，是正常的纯合子胚胎，表明心室腔发育的遗传独立性。肝分化明显但短暂延迟，但组织学和形态学正常。这些结果归因于RXR α基因在胚胎发育中的重要功能，并提供了在其预测的激素反应途径之一中需要RXR的第一个证据。
We have established a targeted loss of-function mutation in the RXR alpha gene in the mouse germ line that results in embryonic lethality between E13.5 and E16.5 when bred to homozygosity. The major defect responsible for lethality is hypoplastic development of the ventricular chambers of the heart, which is manifest as a grossly thinned ventricular wall with concurrent defects in ventricular septation. This phenotype is identical to a subset of the effects of embryonic vitamin A deficiency and, therefore, establishes RXR alpha as a genetic component of the vitamin A signaling pathway in cardiac morphogenesis. The cardiac outflow tracts and associated vessels, which are populated by derivatives of the neural crest and which are also sensitive to vitamin A deficiency, are normal in homozygous embryos, indicating the genetic independence of ventricular chamber development. Hepatic differentiation was dramatically but transiently retarded yet is histologically and morphologically normal. These results ascribe an essential function for the RXR alpha gene in embryonic development and provide the first evidence of a requirement for RXR in one of its predicted hormone response pathways.