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Series GSE47794 Query DataSets for GSE47794
Status Public on Dec 01, 2013
Title Compound loss of muscleblind-like function in myotonic dystrophy
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Myotonic dystrophy (DM) is a multi-systemic disease that severely impacts cardiac and skeletal muscle functions as well as the central nervous system. DM is unusual because it is RNA-mediated disease due to the expression of C(C)UG expansion RNAs that inhibit the activities of the muscleblind-like (MBNL) proteins. In mice, studies using Mbnl1 and Mbnl2 single knockouts have revealed that Mbnl1 plays a predominant role in skeletal and heart muscle alternative splicing regulation while Mbnl2 performs an analogous splicing function in the brain. However, Mbnl single knockout models fail to recapitulate the full-range of adult-onset DM muscle symptoms. Here, we report that Mbnl1; Mbnl2 double knockouts are embryonic lethal while Mbnl1-/-; Mbnl2+/- mice, which express no Mbnl1 and reduced levels of Mbnl2, are viable but develop cardinal features of adult-onset DM cardiac and skeletal muscle disease including reduced lifespan, heart conduction block, severe myotonia and progressive skeletal muscle weakness. Mbnl2 protein levels are elevated in both Mbnl1-/- and Mbnl1-/-; Mbnl2+/- knockouts where Mbnl2 targets Mbnl1-regulated exons. These findings support the MBNL loss-of-function model for DM and provide novel Mbnl compound knockout models to investigate the molecular pathways disrupted by RNA-mediated disease.
Overall design Mbnl2 protein-RNA interactions were assessed in 4-month-old WT and Mbnl1-/- quadriceps muscles in triplicates by HITS-CLIP.
Contributor(s) Manchanda M
Citation(s) 24293317
Submission date Jun 10, 2013
Last update date May 15, 2019
Contact name Maurice Swanson
Phone 3522738076
Organization name University of Florida
Department Molecular Genetics and Microbiology
Lab 220G
Street address 2033 Mowry Road
City Gainesville
State/province Fl
ZIP/Postal code 32608
Country USA
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (2)
GSM1159716 WT, reps 1-3
GSM1159717 Mbnl1-/-, reps 1-3
BioProject PRJNA207816
SRA SRP024393

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Supplementary file Size Download File type/resource
GSE47794_RAW.tar 12.8 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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