Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture
Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture
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DOI：
10.1101/gad.11.23.3143
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发表时间：
1997-12-01
影响因子：
10.5
通讯作者：
Wiche, G
中科院分区：
文献类型：
--
作者：
Andra, K;Lassmann, H;Wiche, G
先前的研究表明，plectin是一种多用途的细胞骨架连接蛋白，在维持多种细胞和组织的结构完整性方面具有重要作用。为了确定凝集素在生物体中的功能，我们在老鼠体内破坏了它的基因。Plectin（-/-）小鼠在出生后2-3天死亡，表现为角质形成细胞变性引起的皮肤起泡。超微结构上半端粒和桥粒未受影响。然而，在缺乏凝集素的小鼠中，半脂酶体的数量明显减少，其机械稳定性明显改变。这些小鼠的皮肤表型与患有单纯大疱性表皮松解症(EBS)-MD的患者相似，这是一种遗传性皮肤起泡疾病，伴有肌肉萎缩，由plectin基因缺陷引起。此外，plectin（-/-）小鼠显示异常，使人联想到骨骼肌的小核性肌病和心脏嵌套椎间盘的解体。我们的结果清楚地证明了粘附素在强化机械应力细胞中的一般作用。Plectin（-/-）小鼠将为研究EBS-MD以及其他类型的包括骨骼肌和心肌的Plectin相关的肌病提供一个有用的工具。
Previous studies suggest that plectin, a versatile cytoskeletal linker protein, has an important role in maintaining the structural integrity of diverse cells and tissues. To establish plectin's function in a living organism, we have disrupted its gene in mice. Plectin (-/-) mice died 2-3 days after birth exhibiting skin blistering caused by degeneration of keratinocytes. Ultrastructurally, hemidesmosomes and desmosomes appeared unaffected. In plectin-deficient mice, however, hemidesmosomes were found to be significantly reduced in number and apparently their mechanical stability was altered. The skin phenotype of these mice was similar to that of patients suffering from epidermolysis bullosa simplex (EBS)-MD, a hereditary skin blistering disease with muscular dystrophy, caused by defects in the plectin gene. In addition, plectin (-/-) mice revealed abnormalities reminiscent of minicore myopathies in skeletal muscle and disintegration of intercalated discs in heart. Our results clearly demonstrate a general role of plectin in the reinforcement of mechanically stressed cells. Plectin (-/-) mice will provide a useful tool for the study of EBS-MD, and possibly other types of plectin-related myopathies involving skeletal and cardiac muscle, in an organism amenable to genetic manipulation.