CHARACTERIZATION OF PHYSICAL FUNCTION AND EXERCISE TOLERANCE FOR A NOVEL RAT MODEL OF DUCHENNE MUSCULAR DYSTROPHY
H. Furutani, S. Luo, S. Luttrell, D.L. Mack, M.B. Brown
University of Washington, Seattle, WA
Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by deficiency of the protein dystrophin and affects approximately 1/3500 boys. Basic/translational studies of exercise effects in DMD have been conducted for decades, but with often contradictory results concerning benefit vs. detriment especially for cardiac muscle. However, these studies have been exclusively performed in a mouse model which does not fully recapitulate the DMD cardiac phenotype. PURPOSE: Here we present the first known characterization of exercise and physical function in a new DMDmdx rat model that better mimics human DMD. METHODS: DMDmdx rats (n=6) and healthy, sibling wild types (WT, n=9) were compared in this study. A battery of functional and exercise tests was performed when the rats were at 14-15 weeks of age, including max treadmill endurance, volitional wheel running distance, forelimb grip strength, and in-vivo hindlimb force testing. RESULTS: Total work performed in treadmill endurance testing was lower for DMDmdx (2.6±0.3 Kpm) vs. WT (29.3±2.2 Kpm), p<0.001. 24-hr wheel running distance was lower for DMDmdx (702±65m) vs. WT (1038±66m), p<0.001. Forelimb grip strength was lower for DMDmdx (211±16g) vs. WT (318±13g), p<0.001. Finally, in electrically-stimulated in-vivo hindlimb force testing, both muscular endurance (% of initial force at 200-s) and peak torque (at 120Hz) were less in DMDmdx(55±2%, 0.33±0.02nM*m/g) vs. WT (69±2%, 0.45±0.030nM*m/g) p<0.01. CONCLUSIONS: Capacity for volitional and forced exercise is severely impaired in the novel DMD rat, congruent with limitations observed in functional muscular strength and endurance. Ongoing work is examining exercise adaptations and cardiac responses in this model which may better represent training responses in DMD patients and be useful for establishing exercise guidelines in this population.
Support provided by a UW Research Royalty Fund awarded to Mary Beth Brown.
Furutani, H; Luo, S; Luttrell, S; Mack, DL; and Brown, MB
"CHARACTERIZATION OF PHYSICAL FUNCTION AND EXERCISE TOLERANCE FOR A NOVEL RAT MODEL OF DUCHENNE MUSCULAR DYSTROPHY,"
International Journal of Exercise Science: Conference Proceedings: Vol. 8:
10, Article 27.
Available at: https://digitalcommons.wku.edu/ijesab/vol8/iss10/27