Heart and head defects in mice lacking pairs of connexins.
Heart and head defects in mice lacking pairs of connexins.
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DOI：
10.1016/j.ydbio.2003.09.036
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发表时间：
2004-01
影响因子：
2.7
通讯作者：
A. Simon;Andrea R. McWhorter;Julie A. Dones;Charity L. Jackson;H. Chen
中科院分区：
文献类型：
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作者：
A. Simon;Andrea R. McWhorter;Julie A. Dones;Charity L. Jackson;H. Chen
小鼠基因消融研究揭示了间隙连接蛋白（连接蛋白）在心脏发育中的作用。在脊椎动物的20种连接蛋白中，有4种在发育中的心脏中表达：连接蛋白37（Cx 37）、连接蛋白40（Cx40）、连接蛋白43（Cx43）和连接蛋白45（Cx45）。虽然每个心脏连接蛋白有不同的表达模式，一些心脏细胞共表达多种连接蛋白在心脏形态发生。由于不同的连接蛋白可能有重叠的功能，一些发育表型可能只有在一个以上的连接蛋白被消融时才变得明显。在这项研究中，我们将Cx40−/−和Cx43−/−小鼠杂交，以产生缺乏Cx40和Cx43的小鼠。Cx40−/−Cx43−/−小鼠在胚胎第12.5天（E12.5）左右死亡，比Cx40−/−或Cx43−/−小鼠早得多，它们表现出畸形的心脏，心室异常旋转，表明有循环缺陷。一些Cx40−/−Cx43−/−动物也会出现露脑畸形的头部缺陷。此外，我们检查了缺乏Cx40和Cx 37的小鼠，发现出生时心房和室间隔缺损的发生率很高。这些结果进一步证明了缝隙连接在胚胎发育中的重要性。此外，消融不同对的心脏连接蛋白会导致不同的心脏缺陷，这表明Cx40、Cx43和Cx 37在心脏形态发生过程中具有共同和独特的功能。
Gene ablation studies in mice have revealed roles for gap junction proteins (connexins) in heart development. Of the 20 connexins in vertebrates, four are expressed in developing heart: connexin37 (Cx37), connexin40 (Cx40), connexin43 (Cx43), and connexin45 (Cx45). Although each cardiac connexin has a different pattern of expression, some heart cells coexpress multiple connexins during cardiac morphogenesis. Since different connexins could have overlapping functions, some developmental phenotypes may only become evident when more than one connexin is ablated. In this study, we interbred Cx40−/−and Cx43−/−mice to generate mice lacking both Cx40 and Cx43. Cx40−/−Cx43−/−mice die around embryonic day 12.5 (E12.5), much earlier than either Cx40−/−or Cx43−/−mice, and they exhibit malformed hearts with ventricles that are abnormally rotated, suggesting a looping defect. Some Cx40−/−Cx43−/−animals also develop head defects characteristic of exencephaly. In addition, we examined mice lacking both Cx40 and Cx37 and found a high incidence of atrial and ventricular septal defects at birth. These results provide further evidence for the importance of gap junctions in embryonic development. Moreover, ablating different pairs of cardiac connexins results in distinct heart defects, suggesting both common and unique functions for Cx40, Cx43, and Cx37 during cardiac morphogenesis.