Date of Award
Level of Access Assigned by Author
Master of Science (MS)
Second Committee Member
Third Committee Member
Duchenne’s Muscular dystrophy (DMD) is a congenital disease of the muscle characterized by muscle atrophy, weakness, and a lower quality of life. Often diagnosed in children, it affects about 1 in every 5,500-7,700 males. A patient diagnosed with DMD is often told to avoid physical activities outside the required amount needed to go on with their day in order to preserve the muscle fibers and integrity. Inactivity in a healthy person leads to decreased muscle mass and increased weakening of the muscle, so we questioned if the effects may be exacerbated in a person diagnosed with DMD having already weakened muscle. In other words, ‘does inactivity make disease progression worse?’ In this project, we explored the effects of inactivity on a zebrafish model of DMD. We used N-Benzyl-p-toluene sulfonamide (BTS), a myosin heavy chain inhibitor, to induce total inactivity for 72-hours consecutively at disease onset (2 days post fertilization), followed by a 72-hour recovery period out of BTS where normal activity is resumed. This setup mimics activity levels that a DMD patient may experience; periods of inactivity advised by doctors to preserve muscle fibers followed by use of the muscle for an activity such as physical therapy. We then analyzed the effects on muscle structure (via birefringence) and function (via swimming distance and velocity), as well as survival. Based on previous studies done on inactivity and muscle health, we hypothesized that extended inactivity would have a deleterious effect on the structure and function of the muscle fibers as well as survival. We found that muscle structure and function was not significantly different than control disease progression after extended inactivity. Survival was also not significantly different from the control. The results of this data show us that while extended inactivity did not worsen disease progression as compared to the control, inactivity did not improve muscle structure and function or survival. This data is an important step in understanding the effects of inactivity on disease progression in DMD in hopes to provide better management and therapy towards DMD.
Driscoll, Sean, "The Effect of BTS Induced Inactivity on a Zebrafish Model of Duchenne Muscular Dystrophy" (2021). Electronic Theses and Dissertations. 3392.