Characterization of Gait Kinematics and Muscle Function in Becker Muscular Dystrophy Pigs: a pilot study

Recently vertebrate animal models of Becker muscular dystrophy (BMD) have been developed. Here, we characterized the gait kinematics and muscle function of a naturally occurring BMD pig model of dystrophin insufficiency. BMD pigs tended to have alterations in joint range of motion (ROM): hip (67%, 95% CI-0.64 to 14.12 degrees), knee (8%, 95% CI-17.14 to 12.13 degrees) and ankle (11%, 95% CI-15 to 8.46 degrees) ROM. While parameters were unaltered in extensor muscles, the dystrophin levels in flexor tibiotarsal joint muscles correlated with fatigue index in BMD pigs. As well as reduced isometric force (48%, 95% CI-1.86 to-0.61 N-m), and a 33% increase in fatigue index (95% CI-36.25 to 96.71 percent); the extensor muscles had no observable reductions in muscle force, with a 48% increase in fatigue index (95% CI - 232.6 to 472.6 percent). Histological analysis of muscle biopsies further supported a BMD phenotype in the flexor muscles of BMD pigs, with a 75% (95% CI-55.14 to-15.66 percent) decrease in large and a 43% (95% CI 17.74 to 57.38 percent) increase in small muscle fiber cross-sectional area. Dystrophin protein abundance was 34% less in flexor muscles from BMD pigs (95% CI-87.9 to 20.2 percent healthy) with a 2.5-fold increase in creatine kinase (CK) levels (95% CI-214 to 1973 pg/dL), and no other abnormalities evident in the blood chemistry profile. Taken together, our model may serve as a clinically relevant model of BMD to assess safety and efficacy of therapeutics.