MONDAY, Nov. 19 (HealthDay News) -- Correcting the splicing defect in the muscle-specific chloride channel (ClC-1) restores channel function and eliminates myotonic discharges in two mouse models of myotonic dystrophy, according to study findings published online Nov. 15 in the Journal of Clinical Investigation.
Thurman M. Wheeler, M.D., from the University of Rochester in Rochester, N.Y., and colleagues examined the effect of using a morpholino antisense oligonucleotide to reverse abnormal alternative splicing of muscle-specific ClC-1 in two mouse models of myotonic dystrophy.
The researchers found that by excluding exon 7a of ClC-1, the mRNA was restored to full-length and upregulated, protein expression was increased at the membrane, ClC-1 function (current density and deactivation kinetics) was normalized, and myotonic discharges were eliminated.
"These observations indicate that the myotonia and chloride channelopathy observed in dystrophia myotonica both result from abnormal alternative splicing of ClC-1 and that antisense-induced exon skipping offers a powerful method for correcting alternative splicing defects in dystrophia myotonica," Wheeler and colleagues conclude.
Abstract
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