Disruption of muscle architecture and myocardial degeneration in mice lacking desmin.
Disruption of muscle architecture and myocardial degeneration in mice lacking desmin.
复制标题
DOI：
10.1083/jcb.134.5.1255
复制
发表时间：
1996-09
影响因子：
7.8
通讯作者：
Capetanaki, Y
中科院分区：
文献类型：
--
作者：
Milner, DJ;Weitzer, G;Tran, D;Bradley, A;Capetanaki, Y
结蛋白是由单个基因编码的肌肉特异性中间丝 (IF) 蛋白，在所有肌肉组织中表达。在成熟的横纹肌中，结蛋白 IF 围绕 Z 盘，将它们连接在一起，并将收缩装置与肌膜和细胞核整合在一起。为了研究结蛋白在体内所有三种肌肉类型中的功能，我们通过同源重组产生了结蛋白缺失小鼠。令人惊讶的是，结蛋白缺失小鼠能够存活并且具有生育能力。然而，这些小鼠表现出涉及心脏、骨骼和平滑肌的多系统疾病。心脏和骨骼肌组织的组织学和电子显微镜分析显示肌肉结构的严重破坏和退化。结构异常包括肌原纤维横向排列丧失和线粒体组织异常。这些异常的后果在心脏中最为严重，表现出心肌进行性变性和坏死，并伴有广泛的钙化。平滑肌异常包括发育不全和变性。目前的数据证明了结蛋白在维持肌原纤维、肌纤维和整个肌肉组织结构和功能完整性中的重要作用，并表明结蛋白的缺乏会导致肌肉退化。
Desmin, the muscle specific intermediate filament (IF) protein encoded by a single gene, is expressed in all muscle tissues. In mature striated muscle, desmin IFs surround the Z-discs, interlink them together and integrate the contractile apparatus with the sarcolemma and the nucleus. To investigate the function of desmin in all three muscle types in vivo, we generated desmin null mice through homologous recombination. Surprisingly, desmin null mice are viable and fertile. However, these mice demonstrated a multisystem disorder involving cardiac, skeletal, and smooth muscle. Histological and electron microscopic analysis in both heart and skeletal muscle tissues revealed severe disruption of muscle architecture and degeneration. Structural abnormalities included loss of lateral alignment of myofibrils and abnormal mitochondrial organization. The consequences of these abnormalities were most severe in the heart, which exhibited progressive degeneration and necrosis of the myocardium accompanied by extensive calcification. Abnormalities of smooth muscle included hypoplasia and degeneration. The present data demonstrate the essential role of desmin in the maintenance of myofibril, myofiber, and whole muscle tissue structural and functional integrity, and show that the absence of desmin leads to muscle degeneration.
登录
查看更多内容
影响因子：
5.6
作者：
ALLEN, RE;RANKIN, LL;PIERCE, PR
通讯作者：
PIERCE, PR
影响因子：
16.2
作者：
GOMI, H;YOKOYAMA, T;ITOHARA, S
通讯作者：
ITOHARA, S
DOI：
10.1083/jcb.82.2.577
发表时间：
1979-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bennett GS;Fellini SA;Toyama Y;Holtzer H
通讯作者：
Holtzer H
影响因子：
7.8
作者：
DANTO, SI;FISCHMAN, DA
通讯作者：
FISCHMAN, DA
DOI：
10.1073/pnas.87.20.7988
发表时间：
1990-10-01
影响因子：
11.1
作者：
CHOI, J;COSTA, ML;HOLTZER, H
通讯作者：
HOLTZER, H