ArticleHuman molecular genetics2018
Temporal and tissue-specific variability of SMN protein levels in mouse models of spinal muscular atrophy.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 80 citations in OpenAlex.
- Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment.The Journal of clinical investigation · 2019Trial
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- Disease-Modifying Therapies in Spinal Muscular Atrophy: Neurodevelopmental and Behavioral Outcomes in the Treatment Era.Advances in therapy · 2026Review
- The role of vascular pathology in SMA: implications for pathogenesis and treatment.Frontiers in cellular neuroscience · 2026Review
- MiR-140-3p regulates axonal motor protein KIF5A and contributes to axonal transport degeneration in SMA.Cell death discovery · 2025Article
- Patient-specific responses toMolecular therapy. Methods & clinical development · 2024Article
- SMN Deficiency Induces an Early Non-Atrophic Myopathy with Alterations in the Contractile and Excitatory Coupling Machinery of Skeletal Myofibers in the SMN∆7 Mouse Model of Spinal Muscular Atrophy.International journal of molecular sciences · 2024Article
- Postnatal management of preterm infants with spinal muscular atrophy: experience from German newborn screening.Orphanet journal of rare diseases · 2024Article
- Characterization of SMA type II skeletal muscle from treated patients shows OXPHOS deficiency and denervation.JCI insight · 2024Article
- Article
- Promoting expression in gene therapy: more is not always better.EMBO molecular medicine · 2024Article
- Long term peripheral AAV9-SMN gene therapy promotes survival in a mouse model of spinal muscular atrophy.Human molecular genetics · 2024Article
- The SMN-ribosome interplay: a new opportunity for Spinal Muscular Atrophy therapies.Biochemical Society transactions · 2024Review
- A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models.Human molecular genetics · 2024Article
- Long-term muscle-specific overexpression of DOK7 in mice using AAV9-tMCK-DOK7.Molecular therapy. Nucleic acids · 2023Article
- Biomarkers in 5q-associated spinal muscular atrophy-a narrative review.Journal of neurology · 2023Review
- Innovating spinal muscular atrophy models in the therapeutic era.Disease models & mechanisms · 2023Article
- Prevalence of morbidities across the lifespan for adults with spinal muscular atrophy: a retrospective cohort study.Orphanet journal of rare diseases · 2023Article
- Base editing rescue of spinal muscular atrophy in cells and in mice.Science (New York, N.Y.) · 2023Article
- Long-TermInternational journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Spinal muscular atrophy (SMA) is a progressive motor neuron disease caused by deleterious variants in SMN1 that lead to a marked decrease in survival motor neuron (SMN) protein expression. Humans have a second SMN gene (SMN2) that is almost identical to SMN1. However, due to alternative splicing the majority of SMN2 messenger ribonucleic acid (mRNA) is translated into a truncated, unstable protein that is quickly degraded. Because the presence of SMN2 provides a unique opportunity for therapy development in SMA patients, the mechanisms that regulate SMN2 splicing and mRNA expression have been elucidated in great detail. In contrast, how much SMN protein is produced at different developmental time points and in different tissues remains under-characterized. In this study, we addressed this issue by determining SMN protein expression levels at three developmental time points across six different mouse tissues and in two distinct mouse models of SMA ('severe' Taiwanese and 'intermediate' Smn2B/- mice). We found that, in healthy control mice, SMN protein expression was significantly influenced by both age and tissue type. When comparing mouse models of SMA, we found that, despite being transcribed from genetically different alleles, control SMN levels were relatively similar. In contrast, the degree of SMN depletion between tissues in SMA varied substantially over time and between the two models. These findings offer an explanation for the differential vulnerability of tissues and organs observed in SMA and further our understanding of the systemic and temporal requirements for SMN with direct relevance for developing effective therapies for 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.