Effect of exercise on limb muscle fiber architecture in a Pompe mouse model (731.4)

Abstract

Pompe disease, a glycogen storage disease causing muscle weakness, is treated by enzyme replacement (ERT). As part of a larger study of exercise effects, we studied the impact of exercise on limb muscle fiber architecture using a mouse knockout model (GAA‐KO) on ERT via gene therapy. Thirty‐seven mice were assigned to 1 of 3 exercise groups: high treadmill (HT), low treadmill (LT), voluntary wheel (WL) vs. sedentary control (SED) and sacrificed after eight weeks. Muscle weight, fiber length (Lf) and in situ sarcomere length were measured and physiologic cross‐sectional area computed for tibialis anterior (TA), gastrocnemius (GA) and soleus (SOL). Initial results: The nonparametric Kruskal‐Wallis revealed significant group differences in Lf for TA (p=.030) and GA (p=.049). Post‐hoc Mann‐Whitney U tests showed significantly longer TA fibers in WL and HT vs. LT (p=.034) and a trend toward longer fibers in WL vs. SED (p=.059). GA fibers were significantly shorter (p=.034) in HT and WL vs. LT. We observed a trend toward shorter GA fibers in HT vs. all other groups and in WL vs. SED (p=.083). Lengthened TA fibers and correspondingly shorter GA fibers may indicate dorsiflexion weakness, as in human infantile onset Pompe disease on ERT, supporting prior concerns about potential negative effect of more strenuous exercise regimens. Further data analysis will continue to explore effects of exercise on muscle strength and function.Grant Funding Source: Supported by R24 HD050837‐01 and NSF BCS 0962677