ArticleHuman molecular genetics2016
Dmpk gene deletion or antisense knockdown does not compromise cardiac or skeletal muscle function in mice.
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 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- 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
- Current biomarker development in myotonic dystrophies.Journal of neurology · 2026Review
- Development of an AAV-delivered microRNA gene therapy for myotonic dystrophy type 1.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Cardiac Involvement in Myotonic Dystrophy Type 1: Mechanisms, Clinical Perspectives, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Differential pathology and susceptibility to MBNL loss across muscles in myotonic dystrophy mouse models.JCI insight · 2025Article
- circARHGAP10 as a candidate biomarker and therapeutic target in myotonic dystrophy type 1.Molecular therapy. Nucleic acids · 2025Article
- Expression levels of core spliceosomal proteins modulate the MBNL-mediated spliceopathy in DM1.Human molecular genetics · 2024Article
- SpecificMolecular therapy. Nucleic acids · 2023Article
- Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development.Human molecular genetics · 2023Article
- Promising AAV.U7snRNAs vectors targetingFrontiers in cell and developmental biology · 2023Article
- Clinical and Molecular Insights into Gastrointestinal Dysfunction in Myotonic Dystrophy Types 1 & 2.International journal of molecular sciences · 2022Review
- Recent Progress and Challenges in the Development of Antisense Therapies for Myotonic Dystrophy Type 1.International journal of molecular sciences · 2022Review
- Systemic DNA/RNA heteroduplex oligonucleotide administration for regulating the gene expression of dorsal root ganglion and sciatic nerve.Molecular therapy. Nucleic acids · 2022Article
- Molecular Therapies for Myotonic Dystrophy Type 1: From Small Drugs to Gene Editing.International journal of molecular sciences · 2022Review
- Overview of the Complex Relationship between Epigenetics Markers, CTG Repeat Instability and Symptoms in Myotonic Dystrophy Type 1.International journal of molecular sciences · 2022Review
- Myotonic dystrophy type 1 embryonic stem cells show decreased myogenic potential, increased CpG methylation at the DMPK locus and RNA mis-splicing.Biology open · 2022Article
- DNA/RNA heteroduplex oligonucleotide technology for regulating lymphocytes in vivo.Nature communications · 2021Article
- Cardiac Pathology in Myotonic Dystrophy Type 1.International journal of molecular sciences · 2021Review
- Molecular mechanisms underlying nucleotide repeat expansion disorders.Nature reviews. Molecular cell biology · 2021Review
- Myotonic dystrophy type 1 drug development: A pipeline toward the market.Drug discovery today · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Myotonic dystrophy type 1 (DM1) is a genetic disorder in which dominant-active DM protein kinase (DMPK) transcripts accumulate in nuclear foci, leading to abnormal regulation of RNA processing. A leading approach to treat DM1 uses DMPK-targeting antisense oligonucleotides (ASOs) to reduce levels of toxic RNA. However, basal levels of DMPK protein are reduced by half in DM1 patients. This raises concern that intolerance for further DMPK loss may limit ASO therapy, especially since mice with Dmpk gene deletion reportedly show cardiac defects and skeletal myopathy. We re-examined cardiac and muscle function in mice with Dmpk gene deletion, and studied post-maturity knockdown using Dmpk-targeting ASOs in mice with heterozygous deletion. Contrary to previous reports, we found no effect of Dmpk gene deletion on cardiac or muscle function, when studied on two genetic backgrounds. In heterozygous knockouts, the administration of ASOs reduced Dmpk expression in cardiac and skeletal muscle by > 90%, yet survival, electrocardiogram intervals, cardiac ejection fraction and muscle strength remained normal. The imposition of cardiac stress by pressure overload, or muscle stress by myotonia, did not unmask a requirement for DMPK. Our results support the feasibility and safety of using ASOs for post-transcriptional silencing of DMPK in muscle and heart.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.