The effects of creatine and exercise on skeletal muscle of FRG1‐transgenic mice

Transgenic overexpression of Fascioscapulohumeral Muscular Dystrophy (FSHD) Region Gene 1 (FRG1) results in severe muscle atrophy and weakness reminiscent of the human disease FSHD. Treatments that act to mitigate muscle dysfunction in the FRG1‐transgenic mouse could hold therapeutic benefit to FSHD patients. Forty FRG1 mice were divided into sedentary, creatine (Cr), and combination creatine and exercise treated groups (CrEx). Creatine was incorporated into standard rat chow at 2% (w/w) and animals exercised in thirty minute bouts at 12–15m/min, three times per week over 52 days. There were no effects of any treatment on bodyweight however quadriceps weight increased 15% in CrEX but not in Cr (P<0.05). CrEX had greater percentage improvements in grip strength (147%, P<0.05) and Rotarod fall speed (204%, P<0.001). As Cr resulted in no functional improvements, the positive effects of CrEX appear to be mediated by exercise, however the potential synergistic action of the combined treatment cannot be excluded. Low intensity exercise attenuates the atrophy and muscle dysfunction associated with FRG1 overexpression, resulting in modest improvements in muscle function. The mechanisms responsible for the beneficial effects of exercise remain to be determined.