Patent ductus arteriosus in mice with smooth muscle-specific Jag1 deletion
Patent ductus arteriosus in mice with smooth muscle-specific Jag1 deletion
复制标题
DOI：
10.1242/dev.052043
复制
发表时间：
2010-12-15
期刊：
影响因子：
4.6
通讯作者：
Gridley, Thomas
中科院分区：
文献类型：
--
作者：
Feng, Xuesong;Krebs, Luke T.;Gridley, Thomas
动脉导管是一种动脉血管，在胎儿期将血液从肺部分流，但通常在出生后闭塞以建立成人循环模式。出生后动脉导管未能闭合称为动脉导管未闭，是最常见的先天性心脏病之一。平滑肌细胞特异性缺失编码Notch配体的Jag 1的小鼠出生后死于动脉导管未闭。这些小鼠在动脉导管和邻近的降主动脉的血管壁中表现出收缩性平滑肌细胞分化的缺陷。这些缺陷是由于无法通过横向诱导在整个血管壁的宽度上传播JAG 1-Notch信号而产生的。异型内皮平滑肌细胞相互作用和同型血管平滑肌细胞相互作用都是动脉导管和相邻降主动脉正常形成和分化所必需的。这种常见先天性心脏病的新模型为动脉导管发育和闭合的遗传程序提供了新的见解。
The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus and is one of the most common congenital heart defects. Mice with smooth muscle cell-specific deletion of Jag1, which encodes a Notch ligand, die postnatally from patent ductus arteriosus. These mice exhibit defects in contractile smooth muscle cell differentiation in the vascular wall of the ductus arteriosus and adjacent descending aorta. These defects arise through an inability to propagate the JAG1-Notch signal via lateral induction throughout the width of the vascular wall. Both heterotypic endothelial smooth muscle cell interactions and homotypic vascular smooth muscle cell interactions are required for normal patterning and differentiation of the ductus arteriosus and adjacent descending aorta. This new model for a common congenital heart defect provides novel insights into the genetic programs that underlie ductus arteriosus development and closure.