Dystrobrevin is a member of the dystrophin protein family that includes homologous proteins utrophin and DRP2. However, dystrobrevin is unique in that it also binds to dystrophin and is part of the dystrophin protein complex. Mice lacking dystrobrevin have a mild muscle myopathy. We used these mice to investigate changes in transcription that occur when dysrobrevin is absent. One transcript that was reduced significantly was NPC1 which encodes the protein associated with Neimann-Pick disease (ref msteen). NPC1 is thought to be involved in the transport of cholesterol and its absence causes neuronal degeneration. We artificially elevated the levels of NPC1 specifically in skeletal muscle of transgenic mice and bred these mice onto the dystrobrevin or dystrophin null (mdx) backgrounds. Elevation of NPC1 reduced the myopathy in both mouse models of dystrophic mice. We continue to investigate the pathways connecting NPC1, cholesterol and muscular dystrophy.
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