Lifetime analysis of mdx skeletal muscle reveals a progressive pathology that leads to myofiber loss
| Autor: | Van-Khoa M. Nguyen, Anna L. Pritchard, Ryan T. Massopust, Dylan A. McCreedy, Young il Lee, Wesley J. Thompson |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
Male Muscle tissue Motor neuron mdx mouse Pathology medicine.medical_specialty Duchenne muscular dystrophy Muscle Fibers Skeletal lcsh:Medicine Neuromuscular junction Article Muscle hypertrophy Cell growth Mice Motor control Animals Humans Medicine Myocyte Muscular dystrophy lcsh:Science Muscle Skeletal Pathological Multidisciplinary business.industry lcsh:R Skeletal muscle medicine.disease Mice Inbred C57BL Muscular Dystrophy Duchenne Disease Models Animal Mechanisms of disease medicine.anatomical_structure Disease Progression lcsh:Q business |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-74192-9 |
| Popis: | The muscular dystrophy X-linked mouse (mdx) is the most commonly used preclinical model for Duchenne muscular dystrophy. Although disease progression in the mouse does not perfectly model the human disease, it shares many pathological features. Early characterizations of the model reported severe pathology through early adulthood followed by disease stabilization. As a result, research in the mdx mouse has largely focused on early adulthood. The overarching goal of this study is to improve the understanding of the mdx mouse model by tracking pathological features of the disease throughout life. We performed a thorough characterization of myofiber pathology in mdx mice from 2 weeks to 2 years of age. We report that individual mdx muscle fibers undergo progressive hypertrophy that continues through the lifespan. Despite massive hypertrophy on the myofiber level, we report no hypertrophy on the muscle level. These seemingly contradictory findings are explained by previously underappreciated myofiber loss in mdx mice. We conclude that due to myofiber loss, in combination with the progressive nature of other pathological features, aged mdx muscle tissue provides reliable benchmarks for disease progression that may be valuable in testing the efficacy of therapeutics for Duchenne muscular dystrophy. |
| Databáze: | OpenAIRE |
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