Restoration of dystrophin‐associated proteins in skeletal muscle of mdx mice transgenic for dystrophin gene

FEBS Letters

Matsumura, Kiichiro¹  Lee, Cheng Chi²  Campbell, Kevin P.¹  Caskey, C.Thomas² 

[1] Howard Hughes Medical Institute and Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242, USA;Institute for Molecular Genetics and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA

关键词: Duchenne muscular dystrophy;    Mdx mouse;    Transgenic mouse;    Dystrophin;    Dystrophin-glycoprotein complex;    Dystrophin-associated protein;   

DOI  :  10.1016/0014-5793(93)80602-Q

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Duchenne muscular dystrophy (DMD) patients and mdx mice are characterized by the absence of dystrophin, a membrane cytoskeletal protein. Dystrophin is associated with a large oligomeric complex of sarcolemmal glycoproteins, including dystroglycan which provides a linkage to the extarcellular matrix component, laminin. The finding that all of the dystrophin-associated proteins (DAPs) are drastically reduced in DMD and mdx skeletal muscle supports the primary function of dystrophin as an anchor of the sarcolemmal glycoprotein complex to the subsarcolemmal cytoskeleton. These findings indicate that the efficacy of dystrophin gene therapy will depend not only on replacing dystrophin but also on restoring all of the DAPs in the sarcolemma. Here we have investigated the status of the DAPs in the skeletal muscle of mdx mice transgenic for the dystrophin gene. Our results demonstrate that transfer of dystrophin gene restores all of the DAPs together with dystrophin, suggesting that dystrophin gene therapy should be effective in restoring the entire dystrophin-glycoprotein complex.

【 授权许可】

Unknown