The role of branched fibres in the pathogenesis of Duchenne muscular dystrophy

Branched fibres are a well-documented phenomenon of regenerating skeletal muscle. They are found in the muscles of boys with Duchenne muscular dystrophy (DMD), a severe condition of progressive muscle wasting caused by an absence of the sarcolemmal protein dystrophin, and in the muscles of themdxmouse, an animal model of DMD. However, only a handful of studies have investigated how the physiological properties of these morphologically deformed fibres differ from those of normal fibres. These studies have found an association between the extent of fibre branching inmdxmuscles and the susceptibility of these muscles to damage from eccentric contractions. They have also found that branchedmdxmuscle fibres cannot sustain maximal contractions in buffered Ca2+ solutions, that branch points are sites of increased mechanical stress and that myofibrillar stucture is greatly disturbed at branch points. These findings have important implications for understanding the function of dystrophin. It is commonly thought that the role of dystrophin is mechanical stabilization of the sarcolemma, as numerous studies have shown that eccentric contractions damagemdxmuscle more than normal muscle. However, the finding that branchedmdxfibres are mechanically weakened raises the question, is it the lack of dystrophin or is it the fibre branching that leads to the vulnerability ofmdxmuscle to contractile damage? The importance of this question to our understanding of the function of dystrophin warrants further research into the physiological properties of branched fibres and how they differ from morphologically normal fibres.