Natural disease history of mouse models for limb girdle muscular dystrophy types 2D and 2F
| Autor: | J. W. Boertje-van der Meulen, M. Overzier, Kayleigh Putker, L. van Vliet, C. L. Tanganyika-de Winter, Annemieke Aartsma-Rus, Jaap J. Plomp, M. van Putten, S. Pasteuning-Vuhman |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Pathology Cardiac fibrosis Respiratory System lcsh:Medicine Gene Expression Myostatin 0302 clinical medicine Tibialis anterior muscle Transforming Growth Factor beta Thoracic Diaphragm Medicine and Health Sciences Morphogenesis Medicine Muscular dystrophy lcsh:Science Musculoskeletal System Multidisciplinary biology Muscles Gastrocnemius Muscles Animal Models Muscle Analysis 3. Good health Bioassays and Physiological Analysis medicine.anatomical_structure Experimental Organism Systems Female Collagen Anatomy medicine.symptom Muscle Regeneration Signal Transduction Research Article medicine.medical_specialty Mice 129 Strain Mouse Models Research and Analysis Methods Thoracic diaphragm 03 medical and health sciences Model Organisms Genetics Animals Regeneration Muscle Skeletal Cardiac Muscles SGCA business.industry lcsh:R Biology and Life Sciences Muscle weakness Muscular Dystrophy Animal Lipid Metabolism medicine.disease Mice Inbred C57BL 030104 developmental biology Muscular Dystrophies Limb-Girdle Skeletal Muscles biology.protein lcsh:Q Transcriptome business Organism Development 030217 neurology & neurosurgery Developmental Biology Limb-girdle muscular dystrophy |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 8, p e0182704 (2017) |
| ISSN: | 1932-6203 |
| Popis: | Limb-girdle muscular dystrophy types 2D and 2F (LGMD 2D and 2F) are autosomal recessive disorders caused by mutations in the alpha- and delta sarcoglycan genes, respectively, leading to severe muscle weakness and degeneration. The cause of the disease has been well characterized and a number of animal models are available for pre-clinical studies to test potential therapeutic interventions. To facilitate transition from drug discovery to clinical trials, standardized procedures and natural disease history data were collected for these mouse models. Implementing the TREAD-NMD standardized operating procedures, we here subjected LGMD2D (SGCA-null), LGMD2F (SGCD-null) and wild type (C57BL/6J) mice to five functional tests from the age of 4 to 32 weeks. To assess whether the functional test regime interfered with disease pathology, sedentary groups were taken along. Muscle physiology testing of tibialis anterior muscle was performed at the age of 34 weeks. Muscle histopathology and gene expression was analysed in skeletal muscles and heart. Muscle histopathology and gene expression was analysed in skeletal muscles and heart. Mice successfully accomplished the functional tests, which did not interfere with disease pathology. Muscle function of SGCA- and SGCD-null mice was impaired and declined over time. Interestingly, female SGCD-null mice outperformed males in the two and four limb hanging tests, which proved the most suitable non-invasive tests to assess muscle function. Muscle physiology testing of tibialis anterior muscle revealed lower specific force and higher susceptibility to eccentric-induced damage in LGMD mice. Analyzing muscle histopathology and gene expression, we identified the diaphragm as the most affected muscle in LGMD strains. Cardiac fibrosis was found in SGCD-null mice, being more severe in males than in females. Our study offers a comprehensive natural history dataset which will be useful to design standardized tests and future pre-clinical studies in LGMD2D and 2F mice |
| Databáze: | OpenAIRE |
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