Stimulation of calcineurin Aα activity attenuates muscle pathophysiology in mdx dystrophic mice

Abstract

Calcineurin activation ameliorates the dystrophic pathology of hindlimb muscles in mdx mice and decreases their susceptibility to contraction damage. In mdx mice, the diaphragm is more severely affected than hindlimb muscles and more representative of Duchenne muscular dystrophy. The constitutively active calcineurin Aα transgene (CnAα) was overexpressed in skeletal muscles of mdx (mdx CnAα*) mice to test whether muscle morphology and function would be improved. Contractile function of diaphragm strips and extensor digitorum longus and soleus muscles from adult mdx CnAα* and mdx mice was examined in vitro. Hindlimb muscles from mdx CnAα* mice had a prolonged twitch time course and were more ..