Restoration of dystrophin expression in cultured hybrid myotubes.
Absence of dystrophin, as found in Duchenne boys, mdx mice and HFMD cats, leads to destabilization of the sarcolemmal-associated protein complex. Gene and cell therapy strategies aim to restore the dystrophin-associated protein complex. In order to better understand the cellular events involved in such therapy in feline and human muscular dystrophy, we asked whether dystrophin-deficient myoblasts would fuse with myoblasts expressing normal dystrophin, and whether the complex would be restored after such a fusion. Cat and human myoblasts were isolated from skeletal muscle of normal subjects and of patients with dystrophin deficiency and proliferated well. After co-culture with normal myoblasts, they fused to form hybrid myotubes. These hybrid myotubes expressed dystrophin, utrophin and dystrophin- associated proteins. Expression of these proteins were restored also in the vicinity of nuclei from dystrophin-deficient donors. These results demonstrate that dystrophin can be expressed and handled normally by hybrid myotubes. They show that myoblasts with a normal dystrophin gene can restore dystrophin expression in dystrophin-deficient myoblasts.
D000818:Animals; D002415:Cats; D018920:Coculture Techniques; D016189:Dystrophin / Q000032:analysis / Q000096:biosynthesis* / Q000172:deficiency*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology*; D012016:Reference Values
D016189:Dystrophin