Muscular degeneration in the absence of dystrophin is a calcium-dependent process.
Duchenne muscular dystrophy (DMD) is a progressive degenerative muscular disease that is due to mutations in the dystrophin gene. Neither the function of dystrophin nor the physiopathology of the disease have been clearly established yet. Several groups have reported elevated calcium concentrations in the mdx mouse model of DMD, but the effect of calcium levels on the progression of the disease continues to be a matter of debate. Here, we show that, in Caenorhabditis elegans, a gain-of-function mutation in the egl-19 calcium channel gene dramatically increases muscle degeneration in dystrophin mutants. Conversely, RNAi-mediated inhibition of egl-19 function reduces muscle degeneration by half. Therefore, our results demonstrate that calcium channel activity is a critical factor in the progression of dystrophin-dependent muscle degeneration.
Mariol
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MC
CGMC, CNRS-UMR 5534, Université Lyon1, 43 bld du 11 Novembre, 69622 Villeurbanne Cedex, France.
Ségalat
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D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009135:Muscular Diseases / Q000209:etiology*; D020388:Muscular Dystrophy, Duchenne / Q000209:etiology; D009154:Mutation
D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D016189:Dystrophin; C109164:Egl-19 protein, C elegans; D009124:Muscle Proteins; D002118:Calcium