DP71 CAN RESTORE THE DYSTROPHIN-ASSOCIATED GLYCOPROTEIN COMPLEX IN MUSCLE BUT FAILS TO PREVENT DYSTROPHY
DP71 CAN RESTORE THE DYSTROPHIN-ASSOCIATED GLYCOPROTEIN COMPLEX IN MUSCLE BUT FAILS TO PREVENT DYSTROPHY
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DOI：
10.1038/ng1294-333
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发表时间：
1994-12-01
期刊：
影响因子：
30.8
通讯作者：
CHAMBERLAIN, JS
中科院分区：
文献类型：
--
作者：
COX, GA;SUNADA, Y;CHAMBERLAIN, JS
已经产生了两个转基因 mdx 小鼠品系，它们在骨骼肌中表达 71 kD 非肌肉肌营养不良蛋白 (Dp71) 亚型。该亚型包含富含半胱氨酸的肌营养不良蛋白和 C 末端结构域，但缺乏 N 末端肌动蛋白结合和中央血影蛋白样重复结构域。 Dp71 与肌膜相关，可恢复肌营养不良蛋白相关糖蛋白复合物所有成员的正常表达和定位。然而，转基因 mdx 小鼠的骨骼肌病理学仍然严重。这些结果表明，肌营养不良蛋白 C 末端不能独立发挥功能来预防营养不良症状，并证实了基于患者数据的预测，即正常肌营养不良蛋白功能需要 N 和 C 末端结构域。
Two lines of transgenic mdx mice have been generated that express a 71 kD non-muscle isoform of dystrophin (Dp71) in skeletal muscle, This isoform contains the cysteine-rich and C-terminal domains of dystrophin, but lacks the N-terminal actin-binding and central spectrin-like repeat domains. Dp71 was associated with the sarcolemma membrane, where it restored normal expression and localization of all members of the dystrophin-associated glycoprotein complex. However, the skeletal muscle pathology of the transgenic mdx mice remained severe. These results indicate that the dystrophin C terminus cannot function independently to prevent dystrophic symptoms and confirms predictions based on patient data that both the N and C-terminal domains are required for normal dystrophin function.