The effect of CRF2R agonist on skeletal muscle in mdx and wildtype mice

Duchenne muscular dystrophy (DMD) is an X‐linked neuromuscular disease resulting in progressive muscle weakness. The mdx mouse is a mouse model of DMD, which lacks dystrophin protein. Corticotrophin releasing factors (CRF) are naturally occurring peptides that bind to a corticotrophin releasing factor receptor (CRFR). It has been reported that a corticotrophin releasing factor receptor 2 (CRF2R) agonist prevented muscle atrophy due to immobilization, denervation and corticosteroid induced atrophy in wildtype (WT) mice. We hypothesized that the CRF2R agonist would increase skeletal muscle and motor performance in mdx mice. WT and mdx mice were divided into two groups: placebo (PL), and CRF2R agonist, delivered via osmotic pump for 8 weeks. Muscles were weighed at time of sacrifice and creatine kinase (CK) activity was measured in serum. CRF2R agonist increased EDL, soleus and tibialis anterior (p<0.05, p<0.01, p<0.01) muscle weight in WT and mdx mice. The mdx mice were heavier than WT mice (p<0.05), while mice on CRF2R agonist were heavier than PL mice (p<0.01). The mdx mice had higher CK activity than WT mice (p<0.01). The mdx PL mice had higher CK activity than mdx CRF2R, WT CRF2R and WT PL mice (p<0.05, p<0.01, p<0.01). We conclude that the CRF2R agonist causes an increase in muscle mass and decrease in CK.