LIMES-Institute, Molecular Genetics, University of Bonn, Bonn, Germany.
Circ Res. 2012 Dec 7;111(12):1528-38. doi: 10.1161/CIRCRESAHA.112.270561. Epub 2012 Sep 14.
The gap junctional protein connexin (Cx) 45 is strongly expressed in the early embryonic myocardium. In the adult hearts of mice and humans, the expression mainly is restricted to the cardiac conduction system. Cx45 plays an essential role for development and function of the embryonic heart because general and cardiomyocyte-directed deficiencies of Cx45 in mice lead to embryonic lethality attributable to morphological and functional cardiovascular defects. The function of Cx45 in the adult mouse has not yet been cleared.
To clarify the function of Cx45 in the adult mouse heart.
To circumvent the embryonic lethality resulting from Cx45 deficiency, mice were generated in which deletion of Cx45 specifically was induced in cardiomyocytes of adult mice. These Cx45-deficient mice were viable but showed a decrease in atrioventricular nodal conductivity. In addition, the Cx30.2 protein that is coexpressed with Cx45 in the cardiac conduction system was posttranscriptionally reduced by 70% in mutant hearts. Furthermore, deletion of both Cx45 and Cx30.2 resulted in viable mice that, however, showed stronger impairment of atrioventricular nodal conduction than the single Cx45-deficient mice.
Cx45 is required for optimal impulse propagation in the atrioventricular node and stabilizes the level of the coexpressed Cx30.2 protein in the adult mouse heart. In contrast to the embryo, Cx45 is not essential for the viability of adult mice.
缝隙连接蛋白 connexin (Cx) 45 在胚胎早期心肌中表达强烈。在成年小鼠和人类的心脏中，其表达主要局限于心脏传导系统。Cx45 对胚胎心脏的发育和功能起着至关重要的作用，因为小鼠中 Cx45 的普遍和心肌细胞靶向缺失会导致胚胎致死，归因于心血管形态和功能缺陷。Cx45 在成年小鼠中的功能尚未明确。
阐明 Cx45 在成年小鼠心脏中的功能。
为了避免因 Cx45 缺失导致的胚胎致死，我们生成了成年小鼠心肌中特异性诱导 Cx45 缺失的小鼠。这些 Cx45 缺失的小鼠是存活的，但房室结传导性降低。此外，在突变心脏中，与 Cx45 在心脏传导系统中共表达的 Cx30.2 蛋白的转录后水平降低了 70%。此外，缺失 Cx45 和 Cx30.2 均导致存活的小鼠，但房室结传导的损害比单独 Cx45 缺失的小鼠更强。
Cx45 是房室结冲动传播的最佳所需，稳定了成年小鼠心脏中共同表达的 Cx30.2 蛋白的水平。与胚胎不同，Cx45 不是成年小鼠存活所必需的。
