| Título: | Severe cardiomyopathy in mice lacking dystrophin and MyoD |
| Autores: |
Megeney, Lynn A. Kablar, Boris Perry, Robert L. S. Ying, Chuyan May, Linda Rudnicki, Michael A. |
| Fecha: | 1999-01-05 |
| Publicador: | The National Academy of Sciences |
| Fuente: |
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| Tipo: | Text |
| Tema: | Biological Sciences |
| Descripción: | 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. |
| Idioma: | en |