ArticleEMBO molecular medicine2013
Pathological impact of SMN2 mis-splicing in adult SMA mice.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- Oligonucleotides targeting the 3' splice site downstream of a microexon as an innovative therapy for autism.NAR molecular medicine · 2025Article
- Correcting tau isoform ratios with a long-acting antisense oligonucleotide alleviates 4R-tauopathy phenotypes.Molecular therapy. Nucleic acids · 2025Article
- Alterations in cardiac function correlate with a disruption in fatty acid metabolism in a mouse model of SMA.Human molecular genetics · 2025Article
- Genetic Variability in Oxidative Stress, Inflammatory, and Neurodevelopmental Pathways: Impact on the Susceptibility and Course of Spinal Muscular Atrophy.Cellular and molecular neurobiology · 2024Article
- TM7SF3 controls TEAD1 splicing to prevent MASH-induced liver fibrosis.Cell metabolism · 2024Article
- Article
- Innovating spinal muscular atrophy models in the therapeutic era.Disease models & mechanisms · 2023Article
- Microvasculopathy in spinal muscular atrophy is driven by a reversible autonomous endothelial cell defect.The Journal of clinical investigation · 2022Article
- Metabolic Dysfunction in Spinal Muscular Atrophy.International journal of molecular sciences · 2021Review
- SMN Depleted Mice Offer a Robust and Rapid Onset Model of Nonalcoholic Fatty Liver Disease.Cellular and molecular gastroenterology and hepatology · 2021Article
- Temperature-sensitive spinal muscular atrophy-causing point mutations lead to SMN instability, locomotor defects and premature lethality inDisease models & mechanisms · 2020Article
- Motor transmission defects with sex differences in a new mouse model of mild spinal muscular atrophy.EBioMedicine · 2020Article
- Mechanisms of Neuronal Alternative Splicing and Strategies for Therapeutic Interventions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Review
- Rescue of spinal muscular atrophy mouse models with AAV9-Exon-specific U1 snRNA.Nucleic acids research · 2019Article
- Low-Intensity Running and High-Intensity Swimming Exercises Differentially Improve Energy Metabolism in Mice With Mild Spinal Muscular Atrophy.Frontiers in physiology · 2019Article
- Risdiplam distributes and increases SMN protein in both the central nervous system and peripheral organs.Pharmacology research & perspectives · 2018Article
- Efficient SMN Rescue following Subcutaneous Tricyclo-DNA Antisense Oligonucleotide Treatment.Molecular therapy. Nucleic acids · 2017Article
- SMN deficiency in severe models of spinal muscular atrophy causes widespread intron retention and DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- RNA-sequencing of a mouse-model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. The related SMN2 gene expresses suboptimal levels of functional SMN protein, due to a splicing defect. Many SMA patients reach adulthood, and there is also adult-onset (type IV) SMA. There is currently no animal model for adult-onset SMA, and the tissue-specific pathogenesis of post-developmental SMN deficiency remains elusive. Here, we use an antisense oligonucleotide (ASO) to exacerbate SMN2 mis-splicing. Intracerebroventricular ASO injection in adult SMN2-transgenic mice phenocopies key aspects of adult-onset SMA, including delayed-onset motor dysfunction and relevant histopathological features. SMN2 mis-splicing increases during late-stage disease, likely accelerating disease progression. Systemic ASO injection in adult mice causes peripheral SMN2 mis-splicing and affects prognosis, eliciting marked liver and heart pathologies, with decreased IGF1 levels. ASO dose-response and time-course studies suggest that only moderate SMN levels are required in the adult central nervous system, and treatment with a splicing-correcting ASO shows a broad therapeutic time window. We describe distinctive pathological features of adult-onset and early-onset SMA.
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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.