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Citations to this article

TorsinA hypofunction causes abnormal twisting movements and sensorimotor circuit neurodegeneration
Chun-Chi Liang, … , Frank Chi, William T. Dauer
Chun-Chi Liang, … , Frank Chi, William T. Dauer
Published June 17, 2014
Citation Information: J Clin Invest. 2014;124(7):3080-3092. https://doi.org/10.1172/JCI72830.
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Research Article Article has an altmetric score of 42

TorsinA hypofunction causes abnormal twisting movements and sensorimotor circuit neurodegeneration

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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 Tor1aflox/–) or isolated CNS expression of DYT1 mutant torsinA (nestin-Cre Tor1aflox/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 Tor1aflox/ΔE compared with nestin-Cre Tor1aflox/– 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.

Authors

Chun-Chi Liang, Lauren M. Tanabe, Stephanie Jou, Frank Chi, William T. Dauer

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 Total
Citations: 2 3 6 7 11 8 5 5 12 17 10 5 91
Citation information
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Citations to this article in year 2017 (12)

Title and authors Publication Year
TorsinA dysfunction causes persistent neuronal nuclear pore defects
SS Pappas, CC Liang, S Kim, CA Rivera, WT Dauer
Human Molecular Genetics 2017
A role for cerebellum in the hereditary dystonia DYT1
R Fremont, A Tewari, C Angueyra, K Khodakhah
eLife 2017
The DYT6 Dystonia Protein THAP1 Regulates Myelination within the Oligodendrocyte Lineage
D Yellajoshyula, CC Liang, SS Pappas, S Penati, A Yang, R Mecano, R Kumaran, S Jou, MR Cookson, WT Dauer
Developmental Cell 2017
TorsinA controls TAN line assembly and the retrograde flow of dorsal perinuclear actin cables during rearward nuclear movement
CA Saunders, NJ Harris, PT Willey, BM Woolums, Y Wang, AJ McQuown, A Schoenhofen, HJ Worman, WT Dauer, GG Gundersen, GW Luxton
The Journal of Cell Biology 2017
Genetic silencing of olivocerebellar synapses causes dystonia-like behaviour in mice
JJ White, RV Sillitoe
Nature Communications 2017
Torsin ATPases: Harnessing Dynamic Instability for Function
AR Chase, E Laudermilch, C Schlieker
Frontiers in Molecular Biosciences 2017
Forebrain knock-out of torsinA reduces striatal free-water and impairs whole-brain functional connectivity in a symptomatic mouse model of DYT1 dystonia
JC DeSimone, SS Pappas, M Febo, RG Burciu, P Shukla, LM Colon-Perez, WT Dauer, DE Vaillancourt
Neurobiology of Disease 2017
Early-onset torsion dystonia: a novel high-throughput yeast genetic screen for factors modifying protein levels of torsinAΔE
LF Zacchi, JC Dittmar, MJ Mihalevic, AM Shewan, BL Schulz, JL Brodsky, KA Bernstein
Disease models & mechanisms 2017
A Role for Dystonia-Associated Genes in Spinal GABAergic Interneuron Circuitry
J Zhang, JA Weinrich, JB Russ, JD Comer, PK Bommareddy, RJ DiCasoli, CV Wright, Y Li, PJ van Roessel, JA Kaltschmidt
Cell Reports 2017
Biallelic TOR1A variants in an infant with severe arthrogryposis
SC Reichert, P Gonzalez-Alegre, GH Scharer
Neurology Genetics 2017
The Anatomical Basis for Dystonia: The Motor Network Model
H A Jinnah, Vladimir Neychev, Ellen J Hess
Tremor and other hyperkinetic movements (New York, N.Y.) 2017
Heterozygous Gnal Mice Are a Novel Animal Model with Which to Study Dystonia Pathophysiology
A Pelosi, F Menardy, D Popa, JA Girault, D Hervé
The Journal of neuroscience : the official journal of the Society for Neuroscience 2017

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