DUCHENNE MUSCULAR-DYSTROPHY AND THE NEUROMUSCULAR-JUNCTION - THE UTROPHIN LINK

Although the precise function of utrophin at the postsynaptic membrane of the neuromuscular junction still remains unclear, despite recent g enetic 'knockout' experiments((1,2)), a separate study in a transgenic mouse model system for Duchenne muscular dystrophy (DMD) has nonethel ess shown that overexpression of utrophin into extrasynaptic regions o f muscle fibers can functionally compensate for the lack of dystrophin and alleviate the muscle pathology((3)). In this context, the next st ep is to identify the mechanisms presiding over expression of utrophin at the neuromuscular synapse in attempts to induce its expression thr oughout DMD muscle fibers. In fact,additional studies have shown that an important DNA element contained with the utrophin promoter may conf er synapse-specific expression to the utrophin gene((4,5)). Identifica tion of the events culminating in the transactivation of the utrophin gene within synaptic myonuclei should provide important cues for the d evelopment of an effective therapeutic strategy for DMD.