ArticleThe Journal of clinical investigation2021
TorsinA restoration in a mouse model identifies a critical therapeutic window for DYT1 dystonia.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Dysregulated nuclear Lamin B1 in DYT1 dystonia thickens nuclear lamina and disrupts 14-3-3 proteins.Cell death discovery · 2026Article
- Dystonia: Insights into Mechanisms and Novel Therapeutics.Current neurology and neuroscience reports · 2026Review
- Validation of a torsinA cerebellar knockdown model of DYT1 dystonia.Dystonia (Lausanne, Switzerland) · 2026Article
- Transcriptomic profiling of DYT-TOR1A patient-derived iPSC reveals dysregulation in extracellular matrix, lipid metabolism, and Chr22q11.23.BMC medical genomics · 2025Article
- Neurobiology of Dystonia: Review of Genetics, Animal Models, and Neuroimaging.Brain sciences · 2025Review
- Emerging Molecular-Genetic Families in Dystonia: Endosome-Autophagosome-Lysosome and Integrated Stress Response Pathways.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- Behavioral signature of trihexyphenidyl in theDystonia (Lausanne, Switzerland) · 2025Article
- TorsinA is essential for neuronal nuclear pore complex localization and maturation.Nature cell biology · 2024Article
- RANBP17 Overexpression Restores Nucleocytoplasmic Transport and Ameliorates Neurodevelopment in Induced DYT1 Dystonia Motor Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Need of orthogonal approaches in neurological disease modeling in mouse.Frontiers in molecular neuroscience · 2024Review
- Disordered network structure and function in dystonia: pathological connectivity vs. adaptive responses.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- TorsinA is essential for the timing and localization of neuronal nuclear pore complex biogenesis.bioRxiv : the preprint server for biology · 2023Article
- Motor deficit and lack of overt dystonia in Dlx conditional Dyt1 knockout mice.Behavioural brain research · 2023Article
- Potential interactions between cerebellar dysfunction and sleep disturbances in dystonia.Dystonia (Lausanne, Switzerland) · 2022Article
- A pathogenic DYT-THAP1 dystonia mutation causes hypomyelination and loss of YY1 binding.Human molecular genetics · 2022Article
- Oligodendrocyte and Extracellular Matrix Contributions to Central Nervous System Motor Function: Implications for Dystonia.Movement disorders : official journal of the Movement Disorder Society · 2022Review
- Molecular Pathology of Laminopathies.Annual review of pathology · 2022Review
- Genetic evidence of aberrant striatal synaptic maturation and secretory pathway alteration in a dystonia mouse model.Dystonia (Lausanne, Switzerland) · 2022Article
- From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
In inherited neurodevelopmental diseases, pathogenic processes unique to critical periods during early brain development may preclude the effectiveness of gene modification therapies applied later in life. We explored this question in a mouse model of DYT1 dystonia, a neurodevelopmental disease caused by a loss-of-function mutation in the TOR1A gene encoding torsinA. To define the temporal requirements for torsinA in normal motor function and gene replacement therapy, we developed a mouse line enabling spatiotemporal control of the endogenous torsinA allele. Suppressing torsinA during embryogenesis caused dystonia-mimicking behavioral and neuropathological phenotypes. Suppressing torsinA during adulthood, however, elicited no discernible abnormalities, establishing an essential requirement for torsinA during a developmental critical period. The developing CNS exhibited a parallel "therapeutic critical period" for torsinA repletion. Although restoring torsinA in juvenile DYT1 mice rescued motor phenotypes, there was no benefit from adult torsinA repletion. These data establish a unique requirement for torsinA in the developing nervous system and demonstrate that the critical period genetic insult provokes permanent pathophysiology mechanistically delinked from torsinA function. These findings imply that to be effective, torsinA-based therapeutic strategies must be employed early in the course of DYT1 dystonia.
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