Roles of forkhead transcription factor Foxc2 (MFH-1) and endothelin receptor A in cardiovascular morphogenesis
Roles of forkhead transcription factor Foxc2 (MFH-1) and endothelin receptor A in cardiovascular morphogenesis
复制标题
DOI：
10.1016/j.cardiores.2004.10.017
复制
发表时间：
2005-02-15
影响因子：
10.8
通讯作者：
Miura, N
中科院分区：
文献类型：
--
作者：
Kanzaki-Kato, N;Tamakoshi, T;Miura, N
目的：Foxc 2/MFH-1是转录因子叉头家族的成员，Foxc 2缺陷小鼠表现出主动脉弓异常（主动脉弓的B型中断）。A型内皮素受体（ETA）是属于G蛋白偶联受体家族的两种已知内皮素受体之一。ETA基因缺陷小鼠的大动脉表现为B型中断的主动脉弓.基于Foxc 2和ETA基因缺陷小鼠心血管系统中相似的表型，我们研究Foxc 2和ETA基因是否在主动脉弓patterning.Methods：Foxc 2和ETA基因杂合子分别杂交获得Foxc 2和ETA纯合子。结果：研究了ETA基因在Foxc 2基因敲除小鼠和ETA基因敲除小鼠中的表达情况，发现Foxc 2和ETA基因的缺失对另一个基因的表达没有影响。接下来，我们分析了缺乏Foxc 2和ETA的小鼠，以检查Foxc 2和ETA之间的关系对体内主动脉弓图案。我们发现，大多数Foxc 2/ETA双突变体胚胎死亡约11.5 dpc和所有存活的小鼠有持续性truncus arteriossus.Conclusions：结果表明，Foxc 2-和ETA-表达细胞相加形成动脉干隔膜。(C)2004年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: Foxc2/MFH-1 is a member of the forkhead family of transcription factors and Foxc2-deficient mice exhibit aortic arch anomalies (type B interruption of the aortic arch). Endothelin receptor type-A (ETA) is one of the two known endothelin receptors that belong to the G-protein-coupled receptor family. ETA-deficient mice show defects in the great arteries, primarily type B interruption of the aortic arch. Based on similar phenotypes in the cardiovascular system of Foxc2- and ETA-deficient mice, we investigated whether Foxc2 and ETA have a close relationship in aortic arch patterning.Methods: The Foxc2 and ETA homozygotes were obtained by crossing the Foxc2 and ETA heterozygotes, respectively. The double Foxc2/ETA homozygotes were obtained by crossing the double Foxc2/ETA heterozygotes.Results: We investigated the expression of ETA in Foxc2-null mice and the expression of Foxc2 in ETA-null mice and found that the absence of either Foxc2 or ETA had no effect on the expression of the other. Next, we analyzed mice lacking both Foxc2 and ETA to examine the relationship between Foxc2 and ETA on aortic arch patterning in vivo. We found that the majority of Foxc2/ETA double-mutant embryos died around 11.5 dpc and that all surviving mice had persistent truncus arteriosus.Conclusions: The results suggest that Foxc2- and ETA-expressing cells additively form the aorticopulmonary septum. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.