Duchenne muscular dystrophy and the neuromuscular junction: the utrophin link

Abstract

Although the precise function of utrophin at the postsynaptic membrane of the neuromuscular junction still remains unclear, despite recent genetic 'knockout' experiments, a separate study in a transgenic mouse model system for Duchenne muscular dystrophy (DMD) has nonetheless shown that overexpression of utrophin into extrasynaptic regions of muscle fibers can functionally compensate for the lack of dystrophin and alleviate the muscle pathology. In this context, the next step is to identify the mechanisms presiding over expression of utrophin at the neuromuscular synapse in attempts to induce its expression throughout DMD muscle fibers. In fact, additional studies have shown that an important DNA element contained with the utrophin promoter may confer synapse-specific expression to the utrophin gene. Identification of the events culminating in the transactivation of the utrophin gene within synaptic myonuclei should provide important cues for the development of an effective therapeutic strategy for DMD.