The absence of dystrophin rather than muscle degeneration causes acetylcholine receptor cluster defects in dystrophic muscle.

Abstract

Duchenne muscular dystrophy is the most common genetic muscle disease. Affected muscles are characterized by abnormal acetylcholine receptor (AChR) clustering. Some studies have suggested that changes in AChR clusters are secondary to degenerative processes. In this study, we demonstrate that AChR cluster fragmentation and muscle degeneration are separate events. We compared AChR clusters and pathological features in mdx mice (mutated dystrophin) and dko mice (mutated dystrophin and utrophin). AChR clusters were identified by binding with α-bungarotoxin, and pathological features were observed by classical immunohistochemical techniques. AChR clusters in mdx and dko mice were reduced in number and exhibited structural fragmentation. However, AChR cluster fragmentation was not significantly different in mdx and dko mice, although more severe inflammatory infiltration and degeneration were observed in dko mice. Furthermore, neuronal nitric oxide synthase, which interacts with dystrophin to anchor itself at the sarcolemma, was notably reduced in mdx and dko mice. Fragmentation of AChR and muscle degeneration are separate events, and both are secondary results of destabilization on the sarcolemma and the cytoskeleton.