Immunochemical study of connectin (titin) in neuromuscular diseases using a monoclonal antibody: connectin is degraded extensively in Duchenne muscular dystrophy

Connectin (also called titin) is a myofibrillar elastic filament which links a thick filament to a neighbouring Z line in a sarcomere and thus contributes significantly to the elastic property of myofibrils. In the present study, the degradation state of connectin in biopsied skeletal muscles from various neuromuscular diseases was investigated by Western blot analysis using a monoclonal antibody which reacts extensively with the degradation products of connectin. In Duchenne muscular dystrophy (DMD), connectin was degraded progressively and relentlessly after 5 years of age. In Becker muscular dystrophy, degradation of connectin was much less than in DMD. Connectin was well preserved in normal controls, and was only minimally degraded in Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, limb girdle muscular dystrophy and myotonic dystrophy, even when the biopsied muscles showed a similar degree of weakness as those of DMD. The degradation of connectin, even though secondary, is presumed to play an important role in the pathogenesis of myofibrillar degeneration in DMD.