title: Electromyographic evidence in support of a knock-in mouse model of DYT1 Dystonia.
abstract: DYT1 dystonia is an autosomal-dominant movement disorder characterized by abnormal, often repetitive, movements and postures. Its hallmark feature is sustained or intermittent contractions of muscles involving co-contractions of antagonist muscle pairs. The symptoms are relieved with the anticholinergic drug trihexyphenidyl. The primary mutation is a trinucleotide deletion (ΔGAG) in DYT1/TOR1A, which codes for torsinA. Previous studies showed that (1) heterozygous Dyt1 ΔGAG knock-in mice, which have an analogous mutation in the endogenous gene, exhibit motor deficits and altered corticostriatal synaptic plasticity in the brain and (2) these deficits can be rescued by trihexyphenidyl. However, brain imaging studies suggest that the Dyt1 knock-in mouse models nonmanifesting mutation carriers of DYT1 dystonia. The aim of this work was to examine the hallmark features of DYT1 dystonia in the Dyt1 knock-in mice by analyzing muscular activities.
  
  
  
  Wireless telemetry devices with biopotential channels were implanted to the bicep and the rectus femori muscles in Dyt1 knock-in mice, and muscular activities were recorded before and after trihexyphenidyl administration.
  
  
  
  (1) Consistent with DYT1 dystonia patients, Dyt1 knock-in mice showed sustained contractions and co-contractions of the antagonistic bicep femoris and rectus femoris. (2) The abnormal muscle contractions were normalized by trihexyphenidyl.
  
  
  
  The results suggest that the motor deficits in Dyt1 knock-in mice are likely produced by abnormal muscle contractions, and Dyt1 knock-in mice can potentially be used as a manifesting disease model to study pathophysiology and develop novel therapeutics. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: Department of Neurology, College of Medicine,, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: DeAndrade
authors.affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, Florida, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Trongnetrpunya
authors.affiliation: Department of Neurology, College of Medicine,, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Yokoi
authors.affiliation: Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Chad C
authors.initials: CC
authors.lastname: Cheetham
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Peng
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Wyss
authors.affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, Florida, USA.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Neurology, College of Medicine,, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D004421:Dystonia; D004422:Dystonia Musculorum Deformans; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D010300:Parkinson Disease
chemical_list: C491548:Dyt1 protein, mouse; D018832:Molecular Chaperones; C108175:TOR1A protein, human
keywords: DYT1; anticholinergic; dystonia; electromyography; muscle contraction