Genetic targeting of Purkinje fibres by Sema3a-CreERT2.

Genetic targeting of Purkinje fibres by Sema3a-CreERT2.
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Sema3a-CreERT2 对浦肯野纤维进行遗传靶向

DOI:
10.1038/s41598-018-20829-9
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发表时间:
2018-02-05
期刊:
影响因子:
4.6
通讯作者:
Zhou B
Zhou B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li Y;Tian X;Zhao H;He L;Zhang S;Huang X;Zhang H;Miquerol L;Zhou B

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心律的维持和兴奋性信号的传导需要通过电活动改变兴奋性信号,并通过工作和传导心肌细胞之间的通信进行协调。了解心室传导系统是如何建立的,为心律失常的病理生理过程提供了新的见解。然而,该领域的主要障碍是缺乏针对心室传导系统浦肯野纤维的特定遗传工具,而没有其他类型的心肌细胞或冠状血管。在这里,我们产生了一个Sema3a-CreERT2敲入小鼠系,以测试其对基因标记的浦肯野纤维的特异性。我们发现Sema3a在胚胎心脏小梁心肌的心内膜下层表达,并且仅限于成人心脏的浦肯野纤维。一项基于Sema3a- creert2系的命运定位研究显示,Sema3a+心肌细胞在围产期仅限于浦肯野纤维的命运,而不是胚胎期。总之,我们的研究提供了一个新的遗传工具,即Sema3a-CreERT2,用于研究调节浦肯野纤维功能的分子机制。
The maintenance of the heart rhythm and the conduction of excitatory signals require changing excitatory signals via electrical activity and coordination by communication between working and conductive cardiomyocytes. Understanding how the ventricular conduction system is established provides novel insights into the pathophysiological progress of cardiac arrhythmias. However, the major hurdle in this field is the lack of a specific genetic tool that targets the Purkinje fibres of the ventricular conduction system and no other types of cardiomyocytes or coronary vessels. Here, we generated a Sema3a-CreERT2 knock-in mouse line to test its specificity for genetically labelled Purkinje fibres. We found that Sema3a was expressed in the subendocardial layer of the trabecular myocardium in the embryonic heart and was restricted to the Purkinje fibres in the adult heart. A fate mapping study based on the Sema3a-CreERT2 line revealed that the Sema3a+ cardiomyocytes were restricted to the fate of Purkinje fibres in the perinatal but not the embryonic stage. Collectively, our study provides a new genetic tool, i.e., Sema3a-CreERT2, for studying the molecular mechanisms that regulate the function of Purkinje fibres.
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