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Skeletal muscle-specific expression of a utrophin transgene rescues utrophin-dystrophin deficient mice
- Source :
- Nature genetics. 19(1)
- Publication Year :
- 1998
-
Abstract
- Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease usually resulting in death of patients by their early twenties. In contrast, mice lacking dystrophin (Dmd(mdx)), appear physically normal despite their underlying muscle pathology. Mice deficient for both dystrophin and the dystrophin-related protein, utrophin, (Dmd(mdx);Utrn-/- mice) die between 6 and 20 weeks of age suffering from severe muscle weakness with joint contractures, pronounced growth retardation and kyphosis, suggesting that dystrophin and utrophin play complementary roles. The exact cause of death in these mice was not determined. Here we show that expression of a truncated utrophin transgene solely within the skeletal muscle of these mutants prevents premature death and the development of any clinical phenotype. In the absence of full-length dystrophin and utrophin, the presence of truncated utrophin also decreases muscle fibre regeneration, relocalizes the dystrophin protein complex to the sarcolemma and re-establishes a normal expression pattern of developmental muscle proteins. These data suggest that Dmd(mdx);Utrn-/- mice succumb to a skeletal muscle defect and that their reduced lifespan is not due to cardiac or neurogenic components. The phenotypic rescue observed demonstrates that the Dmd(mdx);Utrn-/- mice are an ideal model for testing gene delivery protocols for the expression of utrophin or dystrophin in skeletal muscle. To determine the cause of death of the Dmd(mdx):Utrn-/- mice.
- Subjects :
- musculoskeletal diseases
Male
congenital, hereditary, and neonatal diseases and abnormalities
medicine.medical_specialty
Utrophin
animal diseases
Duchenne muscular dystrophy
Transgene
Gene Expression
Dystrophin
Mice
Internal medicine
Genetics
medicine
Animals
Transgenes
Muscle, Skeletal
Mice, Knockout
Sarcolemma
biology
Regeneration (biology)
Muscle weakness
Skeletal muscle
Membrane Proteins
Genetic Therapy
Muscular Dystrophy, Animal
musculoskeletal system
medicine.disease
Immunohistochemistry
Cytoskeletal Proteins
medicine.anatomical_structure
Endocrinology
biology.protein
Female
medicine.symptom
Subjects
Details
- ISSN :
- 10614036
- Volume :
- 19
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature genetics
- Accession number :
- edsair.doi.dedup.....9065865c86636e19a6737547969cfb0b