Effective restoration of dystrophin-associated proteins in vivo by adenovirus-mediated transfer of truncated dystrophin cDNAs.
A series of truncated dystrophin cDNAs (3.1-4.2 kbp) containing only three, three, two or one rod repeats with hinge 1 and 4 (named deltaDysAX2, AX11, AH3, M3, respectively) or no rod repeat retaining either hinge 1 or 4 (named deltaDysH1, H4, respectively) were constructed. These cDNAs were introduced into skeletal muscle of adult mdx mice using the adenovirus vector with a strong CAG promoter. deltaDysAX2, AX11, AH3 and deltaDysM3 expressed themselves successfully and recovered dystrophin-associated proteins effectively. Especially 3.7 kbp cDNA for deltaDysM3 offers the possibility of an approach utilizing newly developed virus vectors, such as an adeno-associated virus vector, toward gene therapy of Duchenne muscular dystrophy.
Yuasa
K
K
Department of Molecular Genetics, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Miyagoe
Y
Y
Yamamoto
K
K
Nabeshima
Y
Y
Dickson
G
G
Takeda
S
S
D000256:Adenoviridae; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D018076:DNA, Complementary; D016189:Dystrophin / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism
D018076:DNA, Complementary; D016189:Dystrophin