Desmoglein 2 mutant mice develop cardiac fibrosis and dilation.
Desmoglein 2 mutant mice develop cardiac fibrosis and dilation.
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DOI：
10.1007/s00395-011-0175-y
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发表时间：
2011-06
影响因子：
9.5
通讯作者：
Leube RE
中科院分区：
文献类型：
--
作者：
Krusche CA;Holthöfer B;Hofe V;van de Sandt AM;Eshkind L;Bockamp E;Merx MW;Kant S;Windoffer R;Leube RE
桥粒是细胞与细胞的粘附位点，也是闰盘的一部分，其连接相邻的心肌细胞。这种连接是由桥粒钙粘蛋白的胞外结构域形成的，这些结构域也与细胞质侧的细胞骨架相连。为了检查桥粒钙粘蛋白桥粒芯糖蛋白 2 对心肌细胞粘附和心脏功能的贡献，制备了缺乏部分桥粒芯糖蛋白 2 细胞外粘附结构域的突变小鼠。大多数活产突变小鼠在 2 周时表现出正常的整体心脏形态。然而，一些动物表现出广泛的纤维化病变。后来，突变体出现心室扩张，导致心功能不全，最终过早死亡。组织学检查发现心肌细胞因钙化坏死而死亡并被纤维组织替代。 2周龄突变体的纤维化病变高度增殖，而较老突变体的纤维化病变几乎没有增殖，表明局部肌肉已被疤痕组织替代。疾病进展与 c-myc、ANF、BNF、CTGF 和 GDF15 mRNA 表达增加相关，这些是心脏应激、重构和心力衰竭的标志物。总而言之，桥粒芯糖蛋白 2 突变小鼠表现出扩张性心肌病和致心律失常性右心室心肌病的特征，这是一种遗传性人类心脏病，具有明显的纤维化和室性心律失常，与包括桥粒芯糖蛋白 2 在内的桥粒蛋白突变有关。本文的在线版本 (doi:10.1007/s00395-011-0175-y) 包含补充内容材料，可供授权用户使用。
Desmosomes are cell–cell adhesion sites and part of the intercalated discs, which couple adjacent cardiomyocytes. The connection is formed by the extracellular domains of desmosomal cadherins that are also linked to the cytoskeleton on the cytoplasmic side. To examine the contribution of the desmosomal cadherin desmoglein 2 to cardiomyocyte adhesion and cardiac function, mutant mice were prepared lacking a part of the extracellular adhesive domain of desmoglein 2. Most live born mutant mice presented normal overall cardiac morphology at 2 weeks. Some animals, however, displayed extensive fibrotic lesions. Later on, mutants developed ventricular dilation leading to cardiac insufficiency and eventually premature death. Upon histological examination, cardiomyocyte death by calcifying necrosis and replacement by fibrous tissue were observed. Fibrotic lesions were highly proliferative in 2-week-old mutants, whereas the fibrotic lesions of older mutants showed little proliferation indicating the completion of local muscle replacement by scar tissue. Disease progression correlated with increased mRNA expression of c-myc, ANF, BNF, CTGF and GDF15, which are markers for cardiac stress, remodeling and heart failure. Taken together, the desmoglein 2-mutant mice display features of dilative cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, an inherited human heart disease with pronounced fibrosis and ventricular arrhythmias that has been linked to mutations in desmosomal proteins including desmoglein 2. The online version of this article (doi:10.1007/s00395-011-0175-y) contains supplementary material, which is available to authorized users.
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影响因子：
9.5
作者：
Ihm, Sang-Hyun;Chang, Kiyuk;Kim, Jae-Hyung
通讯作者：
Kim, Jae-Hyung
影响因子：
9.5
作者：
Hirschy, Alain;Croquelois, Adrien;Ehler, Elisabeth
通讯作者：
Ehler, Elisabeth
影响因子：
39.3
作者：
Basso, Cristina;Czarnowska, Elzbieta;Rampazzo, Alessandra
通讯作者：
Rampazzo, Alessandra
影响因子：
46.9
作者：
Buchholz, F;Angrand, PO;Stewart, AF
通讯作者：
Stewart, AF
DOI：
10.1083/jcb.138.1.193
发表时间：
1997-07-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chitaev NA;Troyanovsky SM
通讯作者：
Troyanovsky SM