Severe cardiomyopathy in mice lacking dystrophin and MyoD
| Autor: | Lynn A. Megeney, Robert L. S. Perry, Boris Kablar, Michael A. Rudnicki, Chuyan Ying, Linda May |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
musculoskeletal diseases
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty mdx mouse Duchenne muscular dystrophy Cardiomegaly Biology MyoD p38 Mitogen-Activated Protein Kinases Dystrophin Mice Internal medicine medicine Animals Regeneration Myocyte Muscle Skeletal Myopathy MyoD Protein Multidisciplinary JNK Mitogen-Activated Protein Kinases Skeletal muscle Biological Sciences Muscular Dystrophy Animal musculoskeletal system medicine.disease Fibrosis Mice Mutant Strains Endocrinology medicine.anatomical_structure Calcium-Calmodulin-Dependent Protein Kinases Mice Inbred mdx biology.protein Mitogen-Activated Protein Kinases medicine.symptom Cardiomyopathies ITGA7 tissues Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:220-225 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | The mdx mouse, a mouse model of Duchenne muscular dystrophy, carries a loss-of-function mutation in dystrophin, a component of the membrane-associated dystrophin–glycoprotein complex. Unlike humans, mdx mice rarely display cardiac abnormalities and exhibit dystrophic changes only in a small number of heavily used skeletal muscle groups. By contrast, mdx:MyoD −/− mice lacking dystrophin and the skeletal muscle-specific bHLH transcription factor MyoD display a severe skeletal myopathy leading to widespread dystrophic changes in skeletal muscle and premature death around 1 year of age. The severely increased phenotype of mdx:MyoD −/− muscle is a consequence of impaired muscle regeneration caused by enhanced satellite cell self-renewal. Here we report that mdx:MyoD −/− mice developed a severe cardiac myopathy with areas of necrosis associated with hypertrophied myocytes. Moreover, heart tissue from mdx:MyoD −/− mice exhibited constitutive activation of stress-activated signaling components, similar to in vitro models of cardiac myocyte adaptation. Taken together, these results support the hypothesis that the progression of skeletal muscle damage is a significant contributing factor leading to development of cardiomyopathy. |
| Databáze: | OpenAIRE |
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