Referenced in: none

Automatically associated channels: ClC1 , ClC4

Title: Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing.

Authors: Nicolas Charlet-B, Rajesh S Savkur, Gopal Singh, Anne V Philips, Elizabeth A Grice, Thomas A Cooper

Journal, date & volume: Mol. Cell, 2002 Jul , 10, 45-53

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12150906

Abstract
Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder caused by a CTG expansion in the 3' untranslated region of the DMPK gene. A predominant characteristic of DM1 is myotonia resulting from skeletal muscle membrane hyperexcitability. Here we demonstrate loss of the muscle-specific chloride channel (ClC-1) mRNA and protein in DM1 skeletal muscle tissue due to aberrant splicing of the ClC-1 pre-mRNA. The splicing regulator, CUG binding protein (CUG-BP), which is elevated in DM1 striated muscle, binds to the ClC-1 pre-mRNA, and overexpression of CUG-BP in normal cells reproduces the aberrant pattern of ClC-1 splicing observed in DM1 skeletal muscle. We propose that disruption of alternative splicing regulation causes a predominant pathological feature of DM1.