Endurance exercise leads to beneficial molecular and physiological effects in a mouse model of myotonic dystrophy type 1
Lydia Sharp MD
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
Department of Neurology, Baylor College of Medicine, Houston, Texas
Present Address: Dr. Sharp's current position is Department of Neurology, Baylor College of Medicine, Houston, Texas.
Lydia Sharp and Diana C. Cox contributed equally to this study and are co-first authors.Search for more papers by this authorDiana C. Cox BA
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, Texas
Lydia Sharp and Diana C. Cox contributed equally to this study and are co-first authors.Search for more papers by this authorCorresponding Author
Thomas A. Cooper MD
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Texas
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas
Correspondence
Thomas A. Cooper, Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030.
Email: [email protected]
Search for more papers by this authorLydia Sharp MD
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
Department of Neurology, Baylor College of Medicine, Houston, Texas
Present Address: Dr. Sharp's current position is Department of Neurology, Baylor College of Medicine, Houston, Texas.
Lydia Sharp and Diana C. Cox contributed equally to this study and are co-first authors.Search for more papers by this authorDiana C. Cox BA
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, Texas
Lydia Sharp and Diana C. Cox contributed equally to this study and are co-first authors.Search for more papers by this authorCorresponding Author
Thomas A. Cooper MD
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Texas
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas
Correspondence
Thomas A. Cooper, Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030.
Email: [email protected]
Search for more papers by this authorPresent Address: Dr. Sharp's current position is Department of Neurology, Baylor College of Medicine, Houston, Texas.
Funding information: National Heart, Lung, and Blood Institute, Grant/Award Number: R01HL045565; National Institute of Arthritis and Musculoskeletal and Skin Diseases, Grant/Award Numbers: 1F31AR073088, R01AR045653, R01AR060733
Abstract
Introduction
Myotonic dystrophy type 1 (DM1) is a multisystemic disease caused by expansion of a CTG repeat in the 3' UTR of the Dystrophia Myotonica-Protein Kinase (DMPK) gene. While multiple organs are affected, more than half of mortality is due to muscle wasting.
Methods
It is unclear whether endurance exercise provides beneficial effects in DM1. Here, we show that a 10-week treadmill endurance exercise program leads to beneficial effects in the HSALR mouse model of DM1.
Results
Animals that performed treadmill training displayed reduced CUGexp RNA levels, improved splicing abnormalities, an increase in skeletal muscle weight and improved endurance capacity.
Discussion
These results indicate that endurance exercise does not have adverse effects in HSALR animals and contributes to beneficial molecular and physiological outcomes.
CONFLICT OF INTEREST
None of the authors has any conflict of interest to disclose.
Supporting Information
| Filename | Description |
|---|---|
| mus26709-sup-0001-FigureS1.tifTIFF image, 5.8 MB | Figure S1 Exercised HSALR animals show no overt changes in skeletal muscle histology. Adult WT or HSALR animals were subjected to either no exercise or treadmill training for a period of 10 weeks. Hematoxylin and eosin staining of quadriceps cross-sections from HSALR sedentary animals show some scattered histological defects at the time point examined (top panel indicated by black arrows, showing areas from three different animals). HSALR exercised animals do not show any additional overt muscle damage. All panels at 20X magnification. Scale bar: 100 μm. |
| mus26709-sup-0002-TableS1.docxWord 2007 document , 73.9 KB | Table S1 Primer sequences for alternative splicing events and Acta1 levels |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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