GRIDLOCK, A LOCALIZED HERITABLE VASCULAR PATTERNING DEFECT IN THE ZEBRAFISH

GRIDLOCK, A LOCALIZED HERITABLE VASCULAR PATTERNING DEFECT IN THE ZEBRAFISH
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DOI:
10.1038/nm1195-1143
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发表时间:
1995-11-01
期刊:
影响因子:
82.9
通讯作者:
FISHMAN, MC
FISHMAN, MC
中科院分区:
医学1区
文献类型:
--
作者:
WEINSTEIN, BM;STEMPLE, DL;FISHMAN, MC

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我们正在使用斑马鱼,Danio rerio,来鉴定产生和形成脊椎动物脉管系统的基因。我们已经分离出一种隐性突变,gridlock(m145)(grl(m145)),其中流向尾部的血液受到局部血管缺陷的阻碍。使用一种新的微血管造影方法,我们表明,封锁是在前干,在那里的成对的外侧背侧腹主动脉通常合并,形成单一的中线主动脉。在大多数突变的胚胎中,动脉-静脉分流和侧支血管发育,绕过病变并重建尾部血流。grl缺陷类似于主动脉缩窄,一种病因不明的人类先天性心血管畸形,在病变的位置和后果以及突变体对侧支血管的依赖性方面。
We are using the zebrafish, Danio rerio, to identify genes that generate and pattern the vertebrate vasculature. We have isolated a recessive mutation, gridlock(m145) (grl(m145)) in which blood flow to the tail is impeded by a localized vascular defect. Using a novel microangiographic method, we show that the blockade is in the anterior trunk, where the paired lateral dorsal aortae normally merge to form the single midline aorta. Arterial-venous shunts and collateral vessels develop in most mutant embryos, bypassing the lesion and reconstituting caudal blood flow. The grl defect resembles coarctation of the aorta, a human congenital cardiovascular malformation of unknown aetiology, in the location of the lesion and its consequences and in the mutants' dependence on collateral vessels for survival.