A muscleblind knockout model for myotonic dystrophy.
Journal:
Science 2003 DecAuthors:
Kanadia RN, Johnstone KA, Mankodi A, Lungu C, Thornton CA, Esson D, Timmers AM, Hauswirth WW, Swanson MS
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 manifestation
...[more]s of DM can result from sequestration of specific RNA binding proteins by a repetitive element expansion in a mutant RNA.[less]
Mesh Headings:
Alternative Splicing, Animals, Cataract, Cell Nucleus, Chloride Channels, DNA-Binding Proteins, Disease Models, Animal, Electromyography, Exons, Gene Targeting, Introns, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Fibers, Skeletal, Muscle Relaxation, Muscle, Skeletal, Myocardium, Myotonic Dystrophy, Protein Isoforms, RNA Splicing, RNA-Binding Proteins, Reverse Transcriptase Polymerase Chain Reaction, Trinucleotide Repeat Expansion, Troponin T