ArticleHuman molecular genetics2022
Mice lacking MBNL1 and MBNL2 exhibit sudden cardiac death and molecular signatures recapitulating myotonic dystrophy.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Cytoplasmic RBM20 granules modulate non-RBM20 target splicing through interactions with other splicing factors.Nucleic acids research · 2026Article
- Progressive cardiac phenotypes and reduced reversibility from long-term CUGexp RNA expression in a DM1 mouse model.JCI insight · 2026Article
- MBNL proteins in health, disease, and therapeutic applications.Nucleic acids research · 2026Review
- Aberrant Splicing ofCirculation. Genomic and precision medicine · 2026Article
- Alternative Splicing of SORBS1 Affects Neuromuscular Junction Integrity in Myotonic Dystrophy Type 1.Journal of cachexia, sarcopenia and muscle · 2025Article
- Transcriptome alterations underlying metabolic dysfunction and liver disease in myotonic dystrophy type 1.Human molecular genetics · 2025Article
- MBNL deficiency in motor neurons disrupts neuromuscular junction maintenance and gait coordination.Brain : a journal of neurology · 2025Article
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- MBNL overexpression rescues cardiac phenotypes in a myotonic dystrophy type 1 heart mouse model.The Journal of clinical investigation · 2025Article
- Influence of CTG repeats from the human DM1 locus on murine gut microbiota.Computational and structural biotechnology journal · 2025Article
- Muscle-driven spinal cord histological and transcriptomic alterations in a myotonic dystrophy mouse model: insights into neuropathy.Brain communications · 2025Article
- MBNL splicing factors regulate the microtranscriptome of skeletal muscles.Nucleic acids research · 2024Article
- RNA-binding proteins in cardiovascular biology and disease: the beat goes on.Nature reviews. Cardiology · 2024Review
- RNA-Binding Proteins in Cardiomyopathies.Journal of cardiovascular development and disease · 2024Review
- RNA binding proteins as mediators of pathological cardiac remodeling.Frontiers in cell and developmental biology · 2024Review
- Cardiac involvement in patient-specific induced pluripotent stem cells of myotonic dystrophy type 1: unveiling the impact of voltage-gated sodium channels.Frontiers in physiology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Myotonic dystrophy (DM) is caused by expansions of C(C)TG repeats in the non-coding regions of the DMPK and CNBP genes, and DM patients often suffer from sudden cardiac death due to lethal conduction block or arrhythmia. Specific molecular changes that underlie DM cardiac pathology have been linked to repeat-associated depletion of Muscleblind-like (MBNL) 1 and 2 proteins and upregulation of CUGBP, Elav-like family member 1 (CELF1). Hypothesis solely targeting MBNL1 or CELF1 pathways that could address all the consequences of repeat expansion in heart remained inconclusive, particularly when the direct cause of mortality and results of transcriptome analyses remained undetermined in Mbnl compound knockout (KO) mice with cardiac phenotypes. Here, we develop Myh6-Cre double KO (DKO) (Mbnl1-/-; Mbnl2cond/cond; Myh6-Cre+/-) mice to eliminate Mbnl1/2 in cardiomyocytes and observe spontaneous lethal cardiac events under no anesthesia. RNA sequencing recapitulates DM heart spliceopathy and shows gene expression changes that were previously undescribed in DM heart studies. Notably, immunoblotting reveals a nearly 6-fold increase of Calsequestrin 1 and 50% reduction of epidermal growth factor proteins. Our findings demonstrate that complete ablation of MBNL1/2 in cardiomyocytes is essential for generating sudden death due to lethal cardiac rhythms and reveal potential mechanisms for DM heart pathogenesis.
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