title: Muscleblind-like 2 (Mbnl2) -deficient mice as a model for myotonic dystrophy.
abstract: 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.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1760, USA.
authors.forename: Minqi
authors.initials: M
authors.lastname: Hao
authors.forename: Kevan
authors.initials: K
authors.lastname: Akrami
authors.forename: Ke
authors.initials: K
authors.lastname: Wei
authors.forename: Carlos
authors.initials: C
authors.lastname: De Diego
authors.forename: Nam
authors.initials: N
authors.lastname: Che
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Ku
authors.forename: James
authors.initials: J
authors.lastname: Tidball
authors.forename: Michael C
authors.initials: MC
authors.lastname: Graves
authors.forename: Perry B
authors.initials: PB
authors.lastname: Shieh
authors.forename: Fabian
authors.initials: F
authors.lastname: Chen
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D018118:Chloride Channels / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D042622:DNA Repeat Expansion / Q000235:genetics; D004576:Electromyography; D005697:Galactosides; D007150:Immunohistochemistry; D007211:Indoles; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000473:pathology*; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018118:Chloride Channels; D017931:DNA Primers; D005697:Galactosides; D007211:Indoles; C529512:Mbnl2 protein, mouse; D016601:RNA-Binding Proteins; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside