Muscle atrophy in titin M-line deficient mice
Muscle atrophy in titin M-line deficient mice
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DOI：
10.1007/s10974-005-9020-y
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发表时间：
2005-12-01
影响因子：
2.7
通讯作者：
Gotthardt, M.
中科院分区：
文献类型：
--
作者：
Peng, J.;Raddatz, K.;Gotthardt, M.
我们使用肌联蛋白敲除模型和一系列技术（包括组织学、原位杂交、电子显微镜和2D凝胶分析）研究了横纹肌中肌联蛋白M线区域缺失的反应。我们发现，肌联蛋白激酶结构域以及肌粒蛋白和MURF-1结合位点的丢失会导致肌节的结构变化，这些变化从M线进行到Z盘，并最终导致肌节解体。这种变化沿着细胞核的中央定位（肌营养不良的标志）、热休克蛋白的上调和蛋白酶体活性的诱导。而比目鱼肌和趾长伸肌的纤维类型组成没有改变，纤维尺寸减小。动物在五周龄时死于肌肉萎缩的并发症。除了肌联蛋白M线区域在任何横纹肌中的结构重要性之外，我们的数据还显示了心脏和骨骼肌之间M线组成的差异如何影响肌节的稳定性和功能。
We investigated the response to deletion of the titin M-line region in striated muscle, using a titin knockout model and a range of techniques that include histology, in situ hybridization, electron microscopy, and 2D gel analysis. We found that the loss of titin's kinase domain and binding sites for myomesin and MURF-1 causes structural changes in the sarcomere that proceed from the M-line to the Z-disc and ultimately result in disassembly of the sarcomere. Disassembly goes along with central localization of nuclei (a hallmark for muscular dystrophy), up-regulation of heat-shock proteins, and induction of proteasome activity. While fiber type composition does not change in soleus and extensor digitorum longus muscle, fiber size is reduced. Animals die from complications of muscle atrophy at five weeks of age. In addition to the structural importance of the titin M-line region in any striated muscle, our data show how differences in M-line composition between heart and skeletal muscle affect sarcomere stability and function.