Mutation of rnf213a by TALEN causes abnormal angiogenesis and circulation defects in zebrafish
Mutation of rnf213a by TALEN causes abnormal angiogenesis and circulation defects in zebrafish
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TALEN 突变 rnf213a 导致斑马鱼异常血管生成和循环缺陷
DOI：
10.1016/j.brainres.2016.04.051
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发表时间：
2016-08-01
期刊：
影响因子：
2.9
通讯作者：
Sheng, Wenli
中科院分区：
文献类型：
--
作者：
Wen, Jun;Sun, Xunsha;Sheng, Wenli
Moyamoya病(MMD)的特征是颈内动脉末端狭窄，脑底血管网络异常。RNF213是东亚人MMD的易感基因。RNF213在MMD发病机制中的作用尚不清楚。在这里，我们利用转录激活物样效应核酸酶(TALEN)技术获得了突变型斑马鱼rnf213a，并描述了斑马鱼MMD胚胎模型的特征。Rnf213a突变斑马鱼在节间血管和头颅次生血管中出现异常血管生成。在电子显微镜下，内皮细胞在细胞与细胞接触正常的情况下表现出形态发生和血管形成的缺陷。躯干和头部的异常萌芽引起了循环障碍。微血管造影显示异常血管内循环减少。尽管结构极其异常，但血管壁没有血流渗透。RNF213a突变体的背主动脉红细胞速度低于野生型同胞。在本研究中，我们提供了一种有希望的MMD体内模型，该模型将有助于了解rnf213a在血管生成中的功能。(C)2016爱思唯尔B.V.保留所有权利。
Moyamoya disease (MMD) is characterized by a stenosis at the terminal of the internal carotid artery and an abnormal vascular network at the base of the brain. RNF213 is a susceptibility gene for MMD in East Asians. The role of RNF213 in the etiology of MMD remains unknown. Here we generated rnf213a mutant zebrafish using transcription activator-like effector nuclease (TALEN) technique and described the characteristics of a zebrafish embryonic model of MMD. rnf213a mutant zebrafish developed abnormal angiogenesis in intersegmental vessels and cranial secondary vessels. Endothelial cells exhibited the defects in morphogenesis and formation of vascular tubes despite normal cell to cell contacts under electron microscope. Circulatory disorder was induced by abnormal sprouts in the trunk and head. Reduced circulation in the abnormal vessels was revealed by microangiography. No blood flow permeated across the vessels wall despite the extremely abnormal structure. rnf213a mutant showed lower erythrocyte velocity in dorsal aorta than that in wild-type siblings. In this study, we provided a promising in vivo model for MMD, and this model would aid to understand the function of rnf213a in angiogenesis. (C) 2016 Elsevier B.V. All rights reserved.