Kanzaki-Kato Naoko, Tamakoshi Tomoki, Fu Yan, Chandra Abhishek, Itakura Tatsuo, Uezato Tadayoshi, Tanaka Toshinobu, Clouthier David E, Sugiyama Toshihiro, Yanagisawa Masashi, Miura Naoyuki
Department of Biochemistry, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Cardiovasc Res. 2005 Feb 15;65(3):711-8. doi: 10.1016/j.cardiores.2004.10.017.
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.
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.
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.
The results suggest that Foxc2- and ETA-expressing cells additively form the aorticopulmonary septum.
Foxc2/MFH-1是叉头转录因子家族的成员，Foxc2基因缺失的小鼠表现出主动脉弓异常（B型主动脉弓中断）。A型内皮素受体（ETA）是已知的两种内皮素受体之一，属于G蛋白偶联受体家族。ETA基因缺失的小鼠在大动脉中表现出缺陷，主要是B型主动脉弓中断。基于Foxc2基因缺失和ETA基因缺失小鼠心血管系统中的相似表型，我们研究了Foxc2和ETA在主动脉弓形成过程中是否存在密切关系。
分别通过将Foxc2杂合子和ETA杂合子杂交获得Foxc2和ETA纯合子。通过将双Foxc2/ETA杂合子杂交获得双Foxc2/ETA纯合子。
我们研究了ETA在Foxc2基因缺失小鼠中的表达以及Foxc2在ETA基因缺失小鼠中的表达，发现Foxc2或ETA的缺失对另一个的表达没有影响。接下来，我们分析了同时缺乏Foxc2和ETA的小鼠，以研究Foxc2和ETA在体内主动脉弓形成中的关系。我们发现大多数Foxc2/ETA双突变胚胎在妊娠第11.5天左右死亡，所有存活的小鼠都有永存动脉干。
结果表明，表达Foxc2和ETA的细胞共同形成主动脉肺动脉隔。
