ArticleThe Journal of clinical investigation2014
TorsinA hypofunction causes abnormal twisting movements and sensorimotor circuit neurodegeneration.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 136 citations in OpenAlex.
- Pathological gain-of-function human variants in the GRIK2 kainate receptor gene cause wide-ranging behavioral dysfunction and seizures in mouse models.Neurobiology of disease · 2026Article
- Transcriptomic profiling of DYT-TOR1A patient-derived iPSC reveals dysregulation in extracellular matrix, lipid metabolism, and Chr22q11.23.BMC medical genomics · 2025Article
- Thalamic deep brain stimulation improves movement in a cerebellar model of lesion-based status dystonicus.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Altered Functional Brain Connectivity in Dyt1 Knock-in mouse models.Dystonia (Lausanne, Switzerland) · 2025Article
- Cerebellar contributions to dystonia: unraveling the role of Purkinje cells and cerebellar nuclei.Dystonia (Lausanne, Switzerland) · 2025Article
- TorsinA is essential for neuronal nuclear pore complex localization and maturation.Nature cell biology · 2024Article
- Sensory-motor circuit is a therapeutic target forScience advances · 2024Article
- Targeting DBS to the centrolateral thalamic nucleus improves movement in a lesion-based model of acquired cerebellar dystonia in mice.bioRxiv : the preprint server for biology · 2024Article
- The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.Brain : a journal of neurology · 2023Article
- Cerebellar Dysfunction as a Source of Dystonic Phenotypes in Mice.Cerebellum (London, England) · 2023Article
- Disordered network structure and function in dystonia: pathological connectivity vs. adaptive responses.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Pathophysiology of Dyt1-Science translational medicine · 2023Article
- TorsinA is essential for the timing and localization of neuronal nuclear pore complex biogenesis.bioRxiv : the preprint server for biology · 2023Article
- DYT-Frontiers in neuroscience · 2023Review
- Dystonia-like behaviors and impaired sensory-motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice.Frontiers in neurology · 2023Article
- Atypical nuclear envelope condensates linked to neurological disorders reveal nucleoporin-directed chaperone activities.Nature cell biology · 2022Article
- Electrophysiological characterization of the striatal cholinergic interneurons inDystonia (Lausanne, Switzerland) · 2022Article
- A dystonia mouse model with motor and sequencing deficits paralleling human disease.Behavioural brain research · 2022Article
- p97/UBXD1 Generate Ubiquitylated Proteins That Are Sequestered into Nuclear Envelope Herniations in Torsin-Deficient Cells.International journal of molecular sciences · 2022Article
- Molecular Pathology of Laminopathies.Annual review of pathology · 2022Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Lack of a preclinical model of primary dystonia that exhibits dystonic-like twisting movements has stymied identification of the cellular and molecular underpinnings of the disease. The classical familial form of primary dystonia is caused by the DYT1 (ΔE) mutation in TOR1A, which encodes torsinA, AAA⁺ ATPase resident in the lumen of the endoplasmic reticular/nuclear envelope. Here, we found that conditional deletion of Tor1a in the CNS (nestin-Cre Tor1a(flox/-)) or isolated CNS expression of DYT1 mutant torsinA (nestin-Cre Tor1a(flox/ΔE)) causes striking abnormal twisting movements. These animals developed perinuclear accumulation of ubiquitin and the E3 ubiquitin ligase HRD1 in discrete sensorimotor regions, followed by neurodegeneration that was substantially milder in nestin-Cre Tor1a(flox/ΔE) compared with nestin-Cre Tor1a(flox/-) animals. Similar to the neurodevelopmental onset of DYT1 dystonia in humans, the behavioral and histopathological abnormalities emerged and became fixed during CNS maturation in the murine models. Our results establish a genetic model of primary dystonia that is overtly symptomatic, and link torsinA hypofunction to neurodegeneration and abnormal twisting movements. These findings provide a cellular and molecular framework for how impaired torsinA function selectively disrupts neural circuits and raise the possibility that discrete foci of neurodegeneration may contribute to the pathogenesis of DYT1 dystonia.
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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.