Gait disturbances in BIO TO‐2 hamster model for muscular dystrophy

BIO TO2 hamster that has a deletion in the delta sarcoglycan gene is an excellent animal model for muscular dystrophy. Gait disturbances, important clinically in patients with muscular dystrophy, have not yet been described in BIO TO2 hamsters. We therefore compared the gait of BIO TO2 dystrophic hamsters with healthy BIO F1B control hamsters using ventral plane videography. Some hamsters were provided access to a voluntary activity wheel for one month prior to study to test whether exercise would affect disease severity. When BIO TO2 and BIO F1B hamsters (12 each) were made to walk on a transparent treadmill belt, we found kinematic and postural changes in BIO TO2 hamsters including significantly shorter swing, stride and stance durations. Stride length was ~13% shorter in BIO TO2 hamsters at 3 and 9 mo. Propulsion duration of the hind limbs, an indicator of muscle strength, was shorter in 9 mo old BIO TO2 hamsters. This deficit was also apparent at 3 mo. Braking duration, reflecting generation of ground reaction forces, was delayed in 9 mo old BIO TO2 hamsters. Hind paw eversion, evidence of muscle weakness, was greater in 9 mo old BIO TO2. The gait disturbances were absent in 3 mo old BIO TO2 hamsters that had access to voluntary wheels, and the stride lengths were comparable to 3 mo old BIO F1B hamsters that had activity wheels. However, comparable gait disturbances were observed in 9 mo old dystrophic hamsters that were provided voluntary wheels for one month. Our findings show that the dystrophic BIO TO2 hamsters recapitulate the functional features of human muscular dystrophy as early as 3 mo of age. Exercise has some benefit in delaying the onset of disease symptoms. Early detection and quantitative measures of gait abnormalities will accelerate the development of new drugs for treating muscular dystrophy.