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Spontaneous Physical activity in a novel mouse model of muscular dystrophy

Abstract

Muscular dystrophy (MD) is an incurable disease characterized by muscle degeneration. MD treatments require use of mouse models in preclinical studies. The DBA/2-congenic Dmdmdx(“D2”) mouse is a novel dystrophic model that is uncharacterized physiologically. PURPOSE: While high intensity physical activity levels declines with MD disease progression, we examined whether 4-month old D2 mice (n=10) engage in less moderate to high intensity physical activity than age-matched controls (“D2J” mice, n=8). METHODS: Physical activity quantification was performed by 0-1 sampling according to a species-specific activity ethnogram of walking, wall pacing, climbing, running and jumping. Activity counts were recorded by a blinded observer every 15-seconds for a 10-minute session (total of 40 observation periods). Individual activity counts were recorded and analyzed in a mouse strain-dependent fashion. An activity-scaled composite metric was also calculated whereby activity sums were scaled for walking and wall pacing (x2), climbing and running (x2.5), and jumping (x3). RESULTS: Scores for individual activities were similar between mouse strains for walking (7% mean group difference, p=0.120), running (61% mean group difference, p=0.145). Moreover, composite metric analyses revealed that scores were not different between mouse strains (D2J 82±36, D2 61±23; p=0.477). In contrast, D2 mice performed 70% less climbing (p=0.049) and 44% less jumping (p=0.046) than D2J mice. CONCLUSION: Findings from composite analysis and some activity counts reveal that D2J controls and D2 congenital dystrophic mice perform statistically similar amounts of physical activity. However, individual activity analyses indicate that D2 mice engage in less climbing and jumping than D2J healthy control mice. Future work should examine these physical activity parameters across the lifespan as related to disease outcomes.

Supported by: Parent Project Muscular Dystrophy to JS and JQ

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