ArticleHuman molecular genetics2019
MBNL1 overexpression is not sufficient to rescue the phenotypes in a mouse model of RNA toxicity.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 20 citations in OpenAlex.
- Comprehensive genomic profiling of mucosal melanoma reveals novel fusion transcripts and dysregulation of cell-cycle, MAPK, and PI3K pathways.The Journal of pathology · 2026Article
- MBNL proteins in health, disease, and therapeutic applications.Nucleic acids research · 2026Review
- Co-Opting MBNL-Dependent Alternative Splicing Cassette Exons to Control Gene Therapy in Myotonic Dystrophy.Annals of neurology · 2026Article
- Multiple Defects in Muscle Regeneration in the HSALR Mouse Model of RNA Toxicity.International journal of molecular sciences · 2025Article
- Promoter-targeted small RNA duplexes increase MBNL1 transcription and mitigate myotonic dystrophy-associated spliceopathy.Nucleic acids research · 2025Article
- MBNL overexpression rescues cardiac phenotypes in a myotonic dystrophy type 1 heart mouse model.The Journal of clinical investigation · 2025Article
- Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle Regeneration.International journal of molecular sciences · 2024Article
- Sustainable recovery of MBNL activity in autoregulatory feedback loop in myotonic dystrophy.Molecular therapy. Nucleic acids · 2022Article
- Mice lacking MBNL1 and MBNL2 exhibit sudden cardiac death and molecular signatures recapitulating myotonic dystrophy.Human molecular genetics · 2022Article
- Myotonic Dystrophies: A Genetic Overview.Genes · 2022Review
- Reversal of RNA toxicity in myotonic dystrophy via a decoy RNA-binding protein with high affinity for expanded CUG repeats.Nature biomedical engineering · 2022Article
- Modeling muscle regeneration in RNA toxicity mice.Human molecular genetics · 2021Article
- Reversible cardiac disease features in an inducible CUG repeat RNA-expressing mouse model of myotonic dystrophy.JCI insight · 2021Article
- TCF4-mediated Fuchs endothelial corneal dystrophy: Insights into a common trinucleotide repeat-associated disease.Progress in retinal and eye research · 2021Review
- Myotonic dystrophy type 2: the 2020 update.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2020Review
- Overexpression of Staufen1 in DM1 mouse skeletal muscle exacerbates dystrophic and atrophic features.Human molecular genetics · 2020Article
- Systemic therapy in an RNA toxicity mouse model with an antisense oligonucleotide therapy targeting a non-CUG sequence within the DMPK 3'UTR RNA.Human molecular genetics · 2020Article
- Molecular Mechanisms of Fuchs and Congenital Hereditary Endothelial Corneal Dystrophies.Reviews of physiology, biochemistry and pharmacology · 2020Review
- AAV-based gene therapies for the muscular dystrophies.Human molecular genetics · 2019Review
- Mitigating RNA Toxicity in Myotonic Dystrophy using Small Molecules.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Myotonic dystrophy type 1 (DM1) is caused by an expanded (CTG)n tract in the 3'UTR of the DM protein kinase (DMPK) gene. The RNA transcripts produced from the expanded allele sequester or alter the function of RNA-binding proteins (MBNL1, CUGBP1, etc.). The sequestration of MBNL1 results in RNA-splicing defects that contribute to disease. Overexpression of MBNL1 in skeletal muscle has been shown to rescue some of the DM1 features in a mouse model and has been proposed as a therapeutic strategy for DM1. Here, we sought to confirm if overexpression of MBNL1 rescues the phenotypes in a different mouse model of RNA toxicity. Using an inducible mouse model of RNA toxicity in which expression of the mutant DMPK 3'UTR results in RNA foci formation, MBNL1 sequestration, splicing defects, myotonia and cardiac conduction defects, we find that MBNL1 overexpression did not rescue skeletal muscle function nor beneficially affect cardiac conduction. Surprisingly, MBNL1 overexpression also did not rescue myotonia, though variable rescue of Clcn1 splicing and other splicing defects was seen. Additionally, contrary to the previous study, we found evidence for increased muscle histopathology with MBNL1 overexpression. Overall, we did not find evidence for beneficial effects from overexpression of MBNL1 as a means to correct RNA toxicity mediated by mRNAs containing an expanded DMPK 3'UTR.
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