Non-toxic ubiquitous over-expression of utrophin in the mdx mouse

Duchenne muscular dystrophy (DMD) is an inherited, severe muscle wasting disease caused by the loss of the cytoskeletal protein, dystrophin. Patients usually die in their late teens or early twenties of cardiac or respiratory failure. We have previously demonstrated that the dystrophin related prote...

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Bibliographic Details
Published in:Neuromuscular disorders : NMD 2001-11, Vol.11 (8), p.713-721
Main Authors: Fisher, Rosie, Tinsley, Jonathon M, Phelps, Steve R, Squire, Sarah E, Townsend, Elizabeth R, Martin, Jo E, Davies, Kay E
Format: Article
Language:English
Subjects:
Aging
Animals
Blotting, Western
Body Weight
Creatinine - urine
Cytoskeletal Proteins - biosynthesis
Cytoskeletal Proteins - genetics
Disease Models, Animal
Disease Progression
Duchenne muscular dystrophy
Dystrophin
Feasibility Studies
Gene Expression
Genetic Therapy
Homozygote
Immunohistochemistry
mdx mouse
Membrane Proteins - biosynthesis
Membrane Proteins - genetics
Mice
Mice, Inbred mdx
Mice, Transgenic
Muscle, Skeletal - metabolism
Muscle, Skeletal - pathology
Muscular Dystrophy, Animal - genetics
Muscular Dystrophy, Animal - metabolism
Muscular Dystrophy, Animal - pathology
Muscular Dystrophy, Animal - therapy
Organ Specificity
Promoter Regions, Genetic
Tissue Distribution - genetics
Transgenes
Up-Regulation - genetics
Utrophin
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Summary:Duchenne muscular dystrophy (DMD) is an inherited, severe muscle wasting disease caused by the loss of the cytoskeletal protein, dystrophin. Patients usually die in their late teens or early twenties of cardiac or respiratory failure. We have previously demonstrated that the dystrophin related protein, utrophin is able to compensate for the loss of dystrophin in the mdx mouse, the mouse model of the disease. Expression of a utrophin transgene under the control of an HSA promoter results in localization of utrophin to the sarcolemma and prevents the muscle pathology. Here we show that the over-expression of full-length utrophin in a broad range of tissues is not detrimental in the mdx mouse. These findings have important implications for the feasibility of the up-regulation of utrophin in therapy for DMD since they suggest that tissue specific up-regulation may not be necessary.
ISSN:0960-8966
1873-2364
DOI:10.1016/S0960-8966(01)00220-6