ArticlePLoS genetics2009
Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy.
Article in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 224 citations in OpenAlex.
- IndividualLife science alliance · 2026Article
- Nanotube-Assisted Motor Neuron and Neuromuscular Junction Stabilization in Spinal Muscular Atrophy: A Hypothesis for Adjunctive Therapy.Neurology international · 2026Review
- Article
- Widespread intron retention and exon skipping characterise alternative splicing changes in a C. elegans model of spinal muscular atrophy.Human molecular genetics · 2026Article
- Neurodegenerative spliceosomopathies.Frontiers in cell and developmental biology · 2026Review
- SMΝΔ7 mice show breathing and airflow defects with significant pathology of respiratory and oral tract tissues.Frontiers in cellular neuroscience · 2026Article
- Extracellular Matrix Remodeling in Motor Neuron Diseases.International journal of molecular sciences · 2025Review
- Glial Cells in Spinal Muscular Atrophy: Speculations on Non-Cell-Autonomous Mechanisms and Therapeutic Implications.Neurology international · 2025Review
- Transcriptome sequencing analysis reveals the molecular mechanism of sepsis-induced muscle atrophy.Journal of thoracic disease · 2024Article
- The SMN-ribosome interplay: a new opportunity for Spinal Muscular Atrophy therapies.Biochemical Society transactions · 2024Review
- Modeling Spinal Muscular Atrophy in Zebrafish: Current Advances and Future Perspectives.International journal of molecular sciences · 2024Review
- Mitigating aberrant Cdk5 activation alleviates mitochondrial defects and motor neuron disease symptoms in spinal muscular atrophy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- PRMT inhibitor promotes SMN2 exon 7 inclusion and synergizes with nusinersen to rescue SMA mice.EMBO molecular medicine · 2023Article
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice.Molecular therapy. Nucleic acids · 2023Article
- A link between agrin signalling and CaScientific reports · 2022Article
- Perspective on automatedNeural regeneration research · 2022Article
- Single-cell RNA sequencing reveals dysregulation of spinal cord cell types in a severe spinal muscular atrophy mouse model.PLoS genetics · 2022Article
- Motor defects in a Drosophila model for spinal muscular atrophy result from SMN depletion during early neurogenesis.PLoS genetics · 2022Article
- Modeling neuromuscular diseases in zebrafish.Frontiers in molecular neuroscience · 2022Review
87 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy is a severe motor neuron disease caused by inactivating mutations in the SMN1 gene leading to reduced levels of full-length functional SMN protein. SMN is a critical mediator of spliceosomal protein assembly, and complete loss or drastic reduction in protein leads to loss of cell viability. However, the reason for selective motor neuron degeneration when SMN is reduced to levels which are tolerated by all other cell types is not currently understood. Widespread splicing abnormalities have recently been reported at end-stage in a mouse model of SMA, leading to the proposition that disruption of efficient splicing is the primary mechanism of motor neuron death. However, it remains unclear whether splicing abnormalities are present during early stages of the disease, which would be a requirement for a direct role in disease pathogenesis. We performed exon-array analysis of RNA from SMN deficient mouse spinal cord at 3 time points, pre-symptomatic (P1), early symptomatic (P7), and late-symptomatic (P13). Compared to littermate control mice, SMA mice showed a time-dependent increase in the number of exons showing differential expression, with minimal differences between genotypes at P1 and P7, but substantial variation in late-symptomatic (P13) mice. Gene ontology analysis revealed differences in pathways associated with neuronal development as well as cellular injury. Validation of selected targets by RT-PCR confirmed the array findings and was in keeping with a shift between physiologically occurring mRNA isoforms. We conclude that the majority of splicing changes occur late in SMA and may represent a secondary effect of cell injury, though we cannot rule out significant early changes in a small number of transcripts crucial to motor neuron survival.
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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.