title: Generation of a novel rodent model for DYT1 dystonia.
abstract: A mutation in the coding region of the Tor1A gene, resulting in a deletion of a glutamic acid residue in the torsinA protein (∆ETorA), is the major cause of the inherited autosomal-dominant early onset torsion dystonia (DYT1). The pathophysiological consequences of this amino acid loss are still not understood. Currently available animal models for DYT1 dystonia provided important insights into the disease; however, they differ with respect to key features of torsinA associated pathology. We developed transgenic rat models harboring the full length human mutant and wildtype Tor1A gene. A complex phenotyping approach including classical behavioral tests, electrophysiology and neuropathology revealed a progressive neurological phenotype in ∆ETorA expressing rats. Furthermore, we were able to replicate key pathological features of torsinA associated pathology in a second species, such as nuclear envelope pathology, behavioral abnormalities and plasticity changes. We therefore suggest that this rat model represents an appropriate new model suitable to further investigate the pathophysiology of ∆ETorA and to test for therapeutic approaches.
authors.affiliation: Dept. of Medical Genetics, University of Tuebingen, Germany. Kathrin.Grundmann@med.uni-tuebingen.de
authors.forename: Kathrin
authors.initials: K
authors.lastname: Grundmann
authors.forename: Nicola
authors.initials: N
authors.lastname: Glöckle
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Martella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sciamanna
authors.forename: Till-Karsten
authors.initials: TK
authors.lastname: Hauser
authors.forename: Libo
authors.initials: L
authors.lastname: Yu
authors.forename: Salvador
authors.initials: S
authors.lastname: Castaneda
authors.forename: Bernd
authors.initials: B
authors.lastname: Pichler
authors.forename: Birgit
authors.initials: B
authors.lastname: Fehrenbacher
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
authors.forename: Brigitte
authors.initials: B
authors.lastname: Nuscher
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.forename: Jasmin
authors.initials: J
authors.lastname: Hettich
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yue
authors.forename: Huu Phuc
authors.initials: HP
authors.lastname: Nguyen
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Thomas
authors.initials: T
authors.lastname: Ott
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004422:Dystonia Musculorum Deformans / Q000235:genetics*; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics*; D051381:Rats; D055647:Rats, Transgenic; D017384:Sequence Deletion
chemical_list: D018832:Molecular Chaperones; C108175:TOR1A protein, human