Requirement of myocardin-related transcription factor-B for remodeling of branchial arch arteries and smooth muscle differentiation
Requirement of myocardin-related transcription factor-B for remodeling of branchial arch arteries and smooth muscle differentiation
复制标题
DOI：
10.1073/pnas.0507346102
复制
发表时间：
2005-10-18
影响因子：
11.1
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Oh, JY;Richardson, JA;Olson, EN
心肌素及其相关转录因子A和B是血清反应因子的共激活因子，在心血管发育中起关键作用。为了确定MRTF-B在体内的功能，我们通过靶向失活MRTF-B基因来产生MRTF-B突变小鼠。我们发现，MRTF-B功能丧失突变纯合子小鼠在妊娠中期死于一系列心血管缺陷，包括鳃弓动脉、右心室双出口、室间隔缺损和薄壁心肌的异常模式。这些异常伴随着鳃弓动脉内的平滑肌细胞分化失败，鳃弓动脉来源于神经嵴。MRTF-B突变小鼠的表型与缺乏心肌素的小鼠不同，揭示了这些血清反应因子共激活因子在体内平滑肌细胞不同亚群发育中的独特作用。
Myocardin and the myocardin-related transcription factors (MRTFs) A and B act as coactivators for serum response factor, which plays a key role in cardiovascular development. To determine the functions of MRTF-B in vivo, we generated MRTF-B mutant mice by targeted inactivation of the MRTF-B gene. We show that mice homozygous for an MRTF-B loss-of-function mutation die during mid-gestation from a spectrum of cardiovascular defects that includes abnormal patterning of the branchial arch arteries, double-outlet right ventricle, ventricular septal defects, and thin-walled myocardium. These abnormalities are accompanied by a failure in differentiation of smooth muscle cells within the branchial arch arteries, which are derived from the neural crest. The phenotype of MRTF-B mutant mice is distinct from that of mice lacking myocardin, revealing unique roles for these serum response factor coactivators in the development of different subsets of smooth muscle cells in vivo.