title: A muscleblind knockout model for myotonic dystrophy.
abstract: The neuromuscular disease myotonic dystrophy (DM) is caused by microsatellite repeat expansions at two different genomic loci. Mutant DM transcripts are retained in the nucleus together with the muscleblind (Mbnl) proteins, and these abnormal RNAs somehow interfere with pre-mRNA splicing regulation. Here, we show that disruption of the mouse Mbnl1 gene leads to muscle, eye, and RNA splicing abnormalities that are characteristic of DM disease. Our results support the hypothesis that manifestations of DM can result from sequestration of specific RNA binding proteins by a repetitive element expansion in a mutant RNA.
authors.affiliation: Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, Gainesville, FL 32610, USA.
authors.forename: Rahul N
authors.initials: RN
authors.lastname: Kanadia
authors.forename: Karen A
authors.initials: KA
authors.lastname: Johnstone
authors.forename: Ami
authors.initials: A
authors.lastname: Mankodi
authors.forename: Codrin
authors.initials: C
authors.lastname: Lungu
authors.forename: Charles A
authors.initials: CA
authors.lastname: Thornton
authors.forename: Douglas
authors.initials: D
authors.lastname: Esson
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Timmers
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.forename: Maurice S
authors.initials: MS
authors.lastname: Swanson
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000067879:CELF1 Protein; D002386:Cataract / Q000209:etiology / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004576:Electromyography; D005091:Exons; D018390:Gene Targeting; D007438:Introns; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009126:Muscle Relaxation; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D020033:Protein Isoforms; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019680:Trinucleotide Repeat Expansion; D020107:Troponin T / Q000235:genetics / Q000378:metabolism
chemical_list: D000067879:CELF1 Protein; C102843:CELF1 protein, human; C086321:CLC-1 channel; D018118:Chloride Channels; D004268:DNA-Binding Proteins; C479922:Mbnl1 protein, mouse; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D020107:Troponin T