权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

EXPRESSION OF DYSTROPHIN AND ITS ASSOCIATED PROTEINS FOLLWING MYOBLAST TRANSPLANTATION INTO MDX MICE.

成肌细胞移植到 MDX 小鼠后肌营养不良蛋白及其相关蛋白的表达。

基本信息

批准号：
07670267
负责人：
HAGIWARA Yasuko
金额：
$ 1.41万
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 Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

Dystropin is a responsible protein of Duchenne muscular dystrophy (DMD) and is present at the protoplasmic surface of normal sarcolemma. Its absencd 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 dystrophin-undercoat in mdx muscle, myoblasts with normal dystrophy gene are injected into mdx mouse muscle. We injected C2 myblasts, a normal mouse muscle cell line, into the muscles of mdx nude mouse. A large number of dystrophin-positive fibers appeared after C2 myoblast transplantation. We examined dystrophin-positive fibers with antidystrophin associated proteins antibodies. We reported that dystrophin-associated proteins are biochemically classified into 3 groups, namely, dystroglycan complex and syntrophin complex. We also cloned a new sarcoglycan (gamma-sarcoglydan) cDNA and showed that the human gamma-sarcoglycan gene was mappetd to chromosome 13q12 and delations that alter its reading frame were identified in three families and one of four sporadic cases of SCARMD.We showed the efficient transduction and expression of lacZ gene in the skeletal muscle of adult C57BL/10ScSn mice after adenovirus-mediated gene transfer. Sixty-two percent of the myofibers in the tibialis anterior (TA) muscle were b-galactosidase-positive after injection of the lacZ gene under the control of the chicken b-actin promoter and the cytomegalovirus enhancer. The transduced gene was preferentially expressed in type IIA and IIX fibers which were richer in oxidative enzymes than type IIB fibers.

Dystropin是Duchenne型肌营养不良症（DMD）的一种致病蛋白，存在于正常肌膜的原生质表面。在DMD和mdx（小鼠相当于DMD）肌肉中观察到其缺失，并被认为是肌纤维变性的原因。将携带正常dystrophy基因的成肌细胞注射到mdx小鼠肌肉中，构建mdx肌肉肌膜下dystrophin-undercoat。我们将正常小鼠肌细胞系C2成肌细胞注射到mdx裸鼠的肌肉中。C2成肌细胞移植后出现大量肌营养不良蛋白阳性纤维。我们用抗肌营养不良蛋白相关蛋白抗体检测肌营养不良蛋白阳性纤维。我们报道了抗肌萎缩蛋白相关蛋白的生物化学分类为3类，即抗肌萎缩蛋白聚糖复合物和突触营养蛋白复合物。我们还克隆了一个新的肌聚糖（gamma-sarcoglycan）cDNA，并在3个SCARMD家系和4个散发病例中发现了人gamma-sarcoglycan基因定位于染色体13 q12，并发现了改变其阅读框架的缺失。在鸡β-肌动蛋白启动子和巨细胞病毒增强子的控制下注射lacZ基因后，胫骨前肌（TA）中62%的肌纤维呈β-半乳糖苷酶阳性。转导的基因优先表达在IIA和IIX型纤维中，这些纤维比IIB型纤维更富含氧化酶。