THE ROLE OF DESMOPLAKIN IN CARDIAC DEVELOPMENT AND DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 桥粒是细胞之间的主要细胞粘附连接，其将细胞膜锚到中间丝网络，并且特别地在经受恒定应力的组织（例如心脏）中发现。桥粒斑蛋白是桥粒复合体的核心成分，在心脏桥粒中高度表达。最近的人类遗传学研究显示，桥粒斑蛋白突变与人类心脏疾病，致瘤性右心室发育不良/心肌病（ARVD/C）有关。尽管有这种意义，桥粒斑蛋白在心脏和ARVD/C中的作用仍然难以捉摸。为了了解桥粒斑蛋白在心脏中的结构和功能作用，我们已经产生了一种新的小鼠模型，该模型有条件地消融心脏中的桥粒斑蛋白，并且正在产生一种携带桥粒斑蛋白的人类突变的小鼠模型。为了确定这些突变小鼠是否存在结构改变，我们想进行TEM和免疫标记研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Desmosomes are major cell adhesion junctions between cells that anchor the cell membrane to the intermediate filament network, and found particularly in tissues undergoing constant stress, such as the heart. Desmoplakin, is a central component of the desmosomal complex, which is highly expressed in the cardiac desmosomes. Recent human genetic studies have revealed that desmoplakin mutations are associated with the human cardiac disease, arrhythmogenic right ventricle dysplasia/cardiomyhopathy (ARVD/C). Despite this implication the role of desmoplakin in the heart and ARVD/C, remains elusive. To understand the structural and functional role of desmoplakin in the heart, we have generated a novel mouse model, which conditionally ablates desmoplakin in the heart and are in the process of generating a mouse model harboring a human mutation of desmoplakin. To determine whether there are structural alterations in these mutant mice, we would like to perform TEM and immunolabeling studies.