ArticleHuman molecular genetics2016
A low absolute number of expanded transcripts is involved in myotonic dystrophy type 1 manifestation in muscle.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Fatty-acid-based antimiR-23b delivery in the DMSXL model: A potential therapeutic strategy for brain dysfunction in myotonic dystrophy type 1.Cell reports. Medicine · 2026Article
- CRISPR/dCas9-mediated tuning of DMPK transcription reveals a quantitative relationship between toxic repeat RNA expression and MBNL1 activity in myotonic dystrophy.Human molecular genetics · 2026Article
- MBNL proteins in health, disease, and therapeutic applications.Nucleic acids research · 2026Review
- Expanding repeats, expanding impact: Somatic instability in myotonic dystrophy type 1.Journal of neuromuscular diseases · 2026Review
- Enhanced muscle uptake of chemically optimized miR-23b antisense oligonucleotides as lead compounds for myotonic dystrophy type 1.American journal of human genetics · 2026Article
- Repeat length as a key determinant for disease severity and antisense oligonucleotide activity in myotonic dystrophy type 1.Molecular therapy. Methods & clinical development · 2025Article
- Characterization ofNAR molecular medicine · 2025Article
- Alternative splicing dysregulation across tissue and therapeutic approaches in a mouse model of myotonic dystrophy type 1.Molecular therapy. Nucleic acids · 2024Article
- Ameliorated cellular hallmarks of myotonic dystrophy in hybrid myotubes from patient and unaffected donor cells.Stem cell research & therapy · 2024Article
- Transcriptome-Wide Studies of RNA-Targeted Small Molecules Provide a Simple and Selective r(CUG)ACS central science · 2023Article
- SpecificMolecular therapy. Nucleic acids · 2023Article
- Block or degrade? Balancing on- and off-target effects of antisense strategies against transcripts with expanded triplet repeats in DM1.Molecular therapy. Nucleic acids · 2023Article
- Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development.Human molecular genetics · 2023Article
- Recent Progress and Challenges in the Development of Antisense Therapies for Myotonic Dystrophy Type 1.International journal of molecular sciences · 2022Review
- Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes.Nature communications · 2022Article
- Regulatory Potential of Competing Endogenous RNAs in Myotonic Dystrophies.International journal of molecular sciences · 2021Review
- Targeted splice sequencing reveals RNA toxicity and therapeutic response in myotonic dystrophy.Nucleic acids research · 2021Article
- Brain Pathogenesis and Potential Therapeutic Strategies in Myotonic Dystrophy Type 1.Frontiers in aging neuroscience · 2021Review
- Three-dimensional imaging in myotonic dystrophy type 1: Linking molecular alterations with disease phenotype.Neurology. Genetics · 2020Article
- Analyzing pre-symptomatic tissue to gain insights into the molecular and mechanistic origins of late-onset degenerative trinucleotide repeat disease.Nucleic acids research · 2020Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Muscular manifestation of myotonic dystrophy type 1 (DM1), a common inheritable degenerative multisystem disorder, is mainly caused by expression of RNA from a (CTG·CAG)n-expanded DM1 locus. Here, we report on comparative profiling of expression of normal and expanded endogenous or transgenic transcripts in skeletal muscle cells and biopsies from DM1 mouse models and patients in order to help us in understanding the role of this RNA-mediated toxicity. In tissue of HSA(LR) mice, the most intensely used 'muscle-only' model in the DM1 field, RNA from the α-actin (CTG)250 transgene was at least 1000-fold more abundant than that from the Dmpk gene, or the DMPK gene in humans. Conversely, the DMPK transgene in another line, DM500/DMSXL mice, was expressed ∼10-fold lower than the endogenous gene. Temporal regulation of expanded RNA expression differed between models. Onset of expression occurred remarkably late in HSA(LR) myoblasts during in vitro myogenesis whereas Dmpk or DMPK (trans)genes were expressed throughout proliferation and differentiation phases. Importantly, quantification of absolute transcript numbers revealed that normal and expanded Dmpk/DMPK transcripts in mouse models and DM1 patients are low-abundance RNA species. Northern blotting, reverse transcriptase-quantitative polymerase chain reaction, RNA-sequencing and fluorescent in situ hybridization analyses showed that they occur at an absolute number between one and a few dozen molecules per cell. Our findings refine the current RNA dominance theory for DM1 pathophysiology, as anomalous factor binding to expanded transcripts and formation of soluble or insoluble ribonucleoprotein aggregates must be nucleated by only few expanded DMPK transcripts and therefore be a small numbers game.
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