Soleus muscle in glycosylation-deficient muscular dystrophy is protected from contraction-induced injury.

The glycosylation of dystroglycan is required for its function as a high-affinity laminin receptor, and loss of dystroglycan glycosylation results in congenital muscular dystrophy. The purpose of this study was to investigate the functional defects in slow- and fast-twitch muscles of glycosylation-deficient Largemyd mice. While a partial alteration in glycosylation of dystroglycan in heterozygous Largemyd/+ mice was not sufficient to alter muscle function, homozygous Largemyd/myd mice demonstrated a marked reduction in specific force in both soleus and extensor digitorum longus (EDL) muscles. Although EDL muscles from Largemyd/myd mice were highly susceptible to lengthening contraction-induced injury, Largemyd/myd soleus muscles surprisingly showed no greater force deficit compared with wild-type soleus muscles even after five lengthening contractions. Despite no increased susceptibility to injury, Largemyd/myd soleus muscles showed loss of dystroglycan glycosylation and laminin binding activity and dystrophic pathology. Interestingly, we show that soleus muscles have a markedly higher sarcolemma expression of β1-containing integrins compared with EDL and gastrocnemius muscles. Therefore, we conclude that β1-containing integrins play an important role as matrix receptors in protecting muscles containing slow-twitch fibers from contraction-induced injury in the absence of dystroglycan function, and that contraction-induced injury appears to be a separable phenotype from the dystrophic pathology of muscular dystrophy.