Coxsackievirus-adenovirus receptor (CAR) is essential for early embryonic cardiac development
Coxsackievirus-adenovirus receptor (CAR) is essential for early embryonic cardiac development
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DOI：
10.1242/jcs.02476
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发表时间：
2005-08-01
影响因子：
4
通讯作者：
Vestweber, D
中科院分区：
文献类型：
--
作者：
Dorner, AA;Wegmann, F;Vestweber, D
柯萨奇病毒-腺病毒受体（CAR）是一种细胞接触蛋白，存在于多种细胞类型中，其生理功能尚不清楚。它属于免疫球蛋白超家族的一个亚家族，其中一些成员是上皮和/或内皮细胞上的连接粘附分子。CAR主要在小鼠的心脏和大脑中表达，直到新生阶段，之后它主要局限于各种上皮细胞。为了更好地了解CAR的生理功能，我们通过基因靶向产生了CAR缺陷小鼠。我们发现这些小鼠在胚胎发育的E11.5和E13.5之间死亡。心肌细胞的超微结构分析显示，肌原纤维的密度降低，它们的方向和捆绑是无序的。此外，线粒体扩大和糖原储存强烈富集。与这些缺陷一致，我们观察到心包水肿形成是心脏功能不足的明显迹象。发育异常可能是基因消融的继发性影响，包括持续的单一房室管和较大血管（如主静脉）的扩张。这些缺陷的继发性得到CAR在血管细胞或血管壁细胞上不表达的事实的支持。未观察到胎盘组织学改变的明显体征。我们得出结论，CAR是胚胎心脏发育所必需的，最有可能是由于其在心肌细胞肌原纤维组织过程中的功能。
The coxsackievirus-adenovirus receptor (CAR) is a cell contact protein on various cell types with unknown physiological function. It belongs to a subfamily of the immunoglobulin-superfamily of which some members are junctional adhesion molecules on epithelial and/or endothelial cells. CAR is dominantly expressed in the hearts and brains of mice until the newborne phase after which it becomes mainly restricted to various epithelial cells. To understand more about the physiological function of CAR, we have generated CAR-deficient mice by gene targeting. We found that these mice die between E11.5 and E13.5 of embryonal development. Ultrastructural analysis of cardiomyocytes; revealed that the density of myofibrils was reduced and that their orientation and bundling was disorganized. In addition, mitochondria were enlarged and glycogen storage strongly enriched. In line with these defects, we observed pericardial edema formation as a clear sign of insufficient heart function. Developmental abnormalities likely to be secondary effects of gene ablation were the persistent singular cardial atrio-ventricular canal and dilatations of larger blood vessels such as the cardinal veins. The secondary nature of these defects was supported by the fact that CAR was not expressed on vascular cells or on cells of the vascular wall. No obvious signs for alterations of the histological organization of the placenta were observed. We conclude that CAR is required for embryonal heart development, most likely due to its function during the organization of myofibrils in cardiomyocytes.