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The Cell Adhesion Molecule M-Cadherin Is Not Essential for Muscle Development and Regeneration

机译:细胞粘附分子M-钙黏着蛋白不是肌肉发育和再生所必需的

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M-cadherin is a classical calcium-dependent cell adhesion molecule that is highly expressed in developing skeletal muscle, satellite cells, and cerebellum. Based on its expression pattern and observations in cell culture, it has been postulated that M-cadherin may be important for the fusion of myoblasts to form myotubes, the correct localization and function of satellite cells during muscle regeneration, and the specialized architecture of adhering junctions in granule cells of cerebellar glomeruli. In order to investigate the potential roles of M-cadherin in vivo, we generated a null mutation in mice. Mutant mice were viable and fertile and showed no gross developmental defects. In particular, the skeletal musculature appeared essentially normal. Moreover, muscle lesions induced by necrosis were efficiently repaired in mutant mice, suggesting that satellite cells are present, can be activated, and are able to form new myofibers. This was also confirmed by normal growth and fusion potential of mutant satellite cells cultured in vitro. In the cerebellum of M-cadherin-lacking mutants, typical contactus adherens junctions were present and similar in size and numbers to the equivalent junctions in wild-type animals. However, the adhesion plaques in the cerebellum of these mutants appeared to contain elevated levels of N-cadherin compared to wild-type animals. Taken together, these observations suggest that M-cadherin in the mouse serves no absolutely required function during muscle development and regeneration and is not essential for the formation of specialized cell contacts in the cerebellum. It seems that N-cadherin or other cadherins can largely compensate for the lack of M-cadherin.
机译:M-钙粘着蛋白是经典的钙依赖性细胞粘附分子,在发育中的骨骼肌,卫星细胞和小脑中高度表达。根据其表达模式和在细胞培养物中的观察结果,推测M-钙粘着蛋白可能对于成肌细胞融合形成肌管,在肌肉再生过程中卫星细胞的正确定位和功能以及粘附连接的特殊结构具有重要意义。在小脑小球的颗粒细胞中。为了研究M-钙粘蛋白在体内的潜在作用,我们在小鼠中产生了空突变。突变小鼠是活的和可育的,并且没有显示出明显的发育缺陷。特别地,骨骼肌组织看起来基本正常。此外,由坏死引起的肌肉损伤在突变小鼠中得到了有效修复,这表明存在卫星细胞,可以激活卫星细胞,并能够形成新的肌纤维。体外培养的突变卫星细胞的正常生长和融合潜力也证实了这一点。在缺少M-钙粘蛋白的突变体的小脑中,存在典型的接触粘附连接,其大小和数量与野生型动物的等效连接相似。但是,与野生型动物相比,这些突变体小脑的粘附斑块似乎含有较高水平的N-钙粘蛋白。综上所述,这些观察结果表明,小鼠中的M-钙粘着蛋白在肌肉发育和再生过程中没有任何绝对必要的功能,对于小脑中专门的细胞接触的形成不是必需的。似乎N-钙粘着蛋白或其他钙粘着蛋白可以很大程度上弥补M-钙粘着蛋白的缺乏。

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