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FORMATION PROCESS OF DYSTROPHIN-POSITIVE MUSCLE FIBERS FOLLOWING THE MYOBLAST TRANSPLANTATION TO MDX MICE.

MDX 小鼠成肌细胞移植后肌营养不良蛋白阳性肌纤维的形成过程。

基本信息

批准号：
05670215
负责人：
HAGIWARA Yasuko
金额：
$ 1.28万
依托单位：
NATIONAL INSTITUTE OF NEUROSCIENCE,NCNP
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Dystrophin is a responsible protein of Duchenne muscular dystrophy(DMD) and is present at the protoplasmic surface of normal sarcolemma. Its absence is observed in DMD and mdx (mouse equivalent to DMD) muscles and is considered to be the cause of muscle fiber degeneration. To construct the subsarcolemmal undercoat in mdx muscle for the trial of therapy of the disease, myoblasts with normal dystrophy gene are injected into mdx mouse muscle. In this study we intended to elucidate the mechanism how dystrophin-positive fibers are constructed following myoblast transfer.We injected C2 myoblasts, a normal mouse muscle cell line, into the muscles of mdx nude mouse. This resulted in wide-spread necrosis of the injected muscle which was followed by regeneration. A large number of dystrophin-positive fibers appeared at the regeneration area. Isoformes of glucose-6-phosphate isomerase homodimer were used for the analysis, which are different in C2 and mdx cells. In dystrophin-positive muscle, a hybrid enzyme was observed, suggesting many of each fiber contain both normal and mdx muclei. Such hybrid fibers may not be resulted from uptake of C2 myoblasts to the intact mdx fibers, but from fusion of C2 myoblasts and mdx satellite cell generated on necrosis of the muscle fibers, considering the fiber formation process and the sizes of these fibers. In addition to this, the presence of muscle fibers made from fusion of C2 myoblasts cannot be excluded.

肌营养不良蛋白是杜氏肌营养不良症（DMD）的一种负责蛋白，存在于正常肌膜的原生质表面。在DMD和mdx（小鼠等效DMD）肌肉中观察到它的缺失，并被认为是肌纤维变性的原因。将正常营养不良基因的成肌细胞注射到mdx小鼠肌肉中，构建mdx肌肉的肌层下内膜，用于治疗mdx疾病的试验。在这项研究中，我们试图阐明成肌细胞转移后肌营养不良蛋白阳性纤维的构建机制。我们将正常小鼠肌肉细胞系C2成肌细胞注射到mdx裸鼠肌肉中。这导致注射的肌肉大面积坏死，随后是再生。再生区出现大量肌营养不良蛋白阳性纤维。葡萄糖-6-磷酸异构酶同二聚体的异构体在C2和mdx细胞中有所不同。在肌营养不良蛋白阳性的肌肉中，观察到一种杂交酶，表明每种纤维的许多同时含有正常和mdx核。考虑到纤维的形成过程和纤维的大小，这种杂交纤维可能不是C2成肌细胞摄取完整的mdx纤维的结果，而是C2成肌细胞与mdx卫星细胞在肌纤维坏死时融合的结果。除此之外，不能排除C2成肌细胞融合形成的肌纤维的存在。