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Muscleblind‐like 2 ( Mbnl2 ) ‐deficient mice as a model for myotonic dystrophy
Author(s) -
Hao Minqi,
Akrami Kevan,
Wei Ke,
De Diego Carlos,
Che Nam,
Ku JeongHee,
Tidball James,
Graves Michael C.,
Shieh Perry B.,
Chen Fabian
Publication year - 2008
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21428
Subject(s) - myotonic dystrophy , myotonia , biology , alternative splicing , rna splicing , trinucleotide repeat expansion , endocrinology , messenger rna , medicine , rna binding protein , skeletal muscle , muscular dystrophy , rna , exon , microbiology and biotechnology , genetics , gene , allele
Myotonic dystrophy (DM), the most common adult‐onset muscular dystrophy, is caused by CTG or CCTG microsatellite repeat expansions. Expanded DM mRNA microsatellite repeats are thought to accumulate in the nucleus, sequester Muscleblind proteins, and interfere with alternative mRNA splicing. Muscleblind2 ( Mbnl2 ) is a member of the family of Muscleblind RNA binding proteins (that also include Mbnl1 and Mbnl3 ) that are known to bind CTG/CCTG RNA repeats. Recently, it was demonstrated that Mbnl1 ‐deficient mice have characteristic features of human DM, including myotonia and defective chloride channel expression. Here, we demonstrate that Mbnl2 ‐deficient mice also develop myotonia and have skeletal muscle pathology consistent with human DM. We also find defective expression and mRNA splicing of the chloride channel (Clcn1) in skeletal muscle that likely contributes to the myotonia phenotype. Our results support the hypothesis that Muscleblind proteins and specifically MBNL2 contribute to the pathogenesis of human DM. Developmental Dynamics 237:403–410, 2008. © 2008 Wiley‐Liss, Inc.