Functional protection of dystrophic mouse (mdx) muscles after adenovirus-mediated transfer of a dystrophin minigene.
Fast skeletal muscles of mdx (X chromosome-linked muscular dystrophy) mice were injected after birth with a recombinant adenovirus containing a minidys- trophin gene, a 6.3-kbp cDNA coding for the N- and C-terminal ends of dystrophin. Adult muscles were challenged by forced lengthening during tetanic contractions. Stretch-induced mechanical and histological damages were much reduced in injected muscles, in direct proportion of the Miniber of fibers expressing minidystrophin. Damaged fibers were preferentially found among minidystrophin-negative regions. Minidystrostrophin confers an important functional and structural protection of limb muscles against high mechanical stress, even after a partial somatic gene transfer.
Deconinck
N
N
Départment de Physiologie, Université Catholique de Louvain, Brussels,Belgium.
Ragot
T
T
Maréchal
G
G
Perricaudet
M
M
Gillis
J M
JM
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016189:Dystrophin / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D066298:In Vitro Techniques; D051379:Mice; D018101:Mice, Inbred mdx; D009119:Muscle Contraction; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D013314:Stress, Mechanical
D016189:Dystrophin