Generation of a novel rodent model for DYT1 dystonia

Kathrin Grundmann, Nicola Glöckle, Giuseppina Martella, Giuseppe Sciamanna, Till Karsten Hauser, Libo Yu, Salvador Castaneda, Bernd Pichler, Birgit Fehrenbacher, Martin Schaller, Brigitte Nuscher, Christian Haass, Jasmin Hettich, Zhenyu Yue, Huu Phuc Nguyen, Antonio Pisani, Olaf Riess, Thomas Ott

Research output: Contribution to journalArticlepeer-review

Abstract

A mutation in the coding region of the . Tor1A gene, resulting in a deletion of a glutamic acid residue in the torsinA protein ({increment}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 increment 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 increment ETorA and to test for therapeutic approaches.

Original languageEnglish
Pages (from-to)61-74
Number of pages14
JournalNeurobiology of Disease
Volume47
Issue number1
DOIs
Publication statusPublished - Jul 2012

Keywords

  • DYT1 dystonia
  • Movement disorder
  • TorsinA
  • Transgenic rat model

ASJC Scopus subject areas

  • Neurology

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