Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder with a high spontaneous mutation rate and no effective treatment, hence development of genetic based therapies is an important goal. We report that expression of a recombinant human minidystrophin cDNA, compatible with current viral vectors, can significantly reduce the myopathic phenotype in transgenic mdx mice, even when expressed at only 20-30% of endogenous dystrophin levels at the sarcolemma. To the extent that data obtained in mouse studies are applicable to DMD, the virtual elimination of morphological and biochemical abnormalities in the mdx mouse supports the use of this cDNA in somatic gene therapy protocols for DMD.
Wells
D J
DJ
Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
Wells
K E
KE
Asante
E A
EA
Turner
G
G
Sunada
Y
Y
Campbell
K P
KP
Walsh
F S
FS
Dickson
G
G
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics / Q000628:therapy; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010641:Phenotype; D017384:Sequence Deletion
D017931:DNA Primers; D018076:DNA, Complementary; D016189:Dystrophin