Generation of a novel rodent model for DYT1 dystonia
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...
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Elsevier
2012-07-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996112000952 |
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doaj-0ea885d0dfe24b3cbffdcfb1f8f91a632021-03-22T12:38:27ZengElsevierNeurobiology of Disease1095-953X2012-07-014716174Generation of a novel rodent model for DYT1 dystoniaKathrin Grundmann0Nicola Glöckle1Giuseppina Martella2Giuseppe Sciamanna3Till-Karsten Hauser4Libo Yu5Salvador Castaneda6Bernd Pichler7Birgit Fehrenbacher8Martin Schaller9Brigitte Nuscher10Christian Haass11Jasmin Hettich12Zhenyu Yue13Huu Phuc Nguyen14Antonio Pisani15Olaf Riess16Thomas Ott17Dept. of Medical Genetics, University of Tuebingen, Germany; Corresponding author at: Dept. of Medical Genetics, University of Tuebingen, Calwer Str. 7, 72076 Tuebingen, Germany. Fax: +49 7071 295228.Dept. of Medical Genetics, University of Tuebingen, GermanyDept. of Neuroscience, University “Tor Vergata”, Rome, Italy; Fondazione Santa Lucia I.R.C.C.S., Rome, ItalyDept. of Neuroscience, University “Tor Vergata”, Rome, Italy; Fondazione Santa Lucia I.R.C.C.S., Rome, ItalyDept. of Neuroradiology, University of Tuebingen, GermanyDept. of Medical Genetics, University of Tuebingen, GermanyDepartment of Preclinical imaging and Radiopharmacy, University Hospital of Tuebingen, GermanyDepartment of Preclinical imaging and Radiopharmacy, University Hospital of Tuebingen, GermanyDept. of Dermatology, University of Tuebingen, GermanyDept. of Dermatology, University of Tuebingen, GermanyGerman Center for Neurodegenerative Diseases, Ludwig Maximilian University Munich, Germany; Adolf-Butenandt-Institute, Biochemistry, Ludwig Maximilian University, GermanyGerman Center for Neurodegenerative Diseases, Ludwig Maximilian University Munich, Germany; Adolf-Butenandt-Institute, Biochemistry, Ludwig Maximilian University, GermanyDept. of Medical Genetics, University of Tuebingen, GermanyDepartment of Neurology & Neuroscience Friedman Brain Institute Mount Sinai School of Medicine New York, NY 10029Dept. of Medical Genetics, University of Tuebingen, GermanyDept. of Neuroscience, University “Tor Vergata”, Rome, Italy; Fondazione Santa Lucia I.R.C.C.S., Rome, ItalyDept. of Medical Genetics, University of Tuebingen, GermanyDept. of Medical Genetics, University of Tuebingen, GermanyA 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.http://www.sciencedirect.com/science/article/pii/S0969996112000952Transgenic rat modelTorsinADYT1 dystoniaMovement disorder |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Generation of a novel rodent model for DYT1 dystonia Neurobiology of Disease Transgenic rat model TorsinA DYT1 dystonia Movement disorder |
| author_facet |
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 |
| author_sort |
Kathrin Grundmann |
| title |
Generation of a novel rodent model for DYT1 dystonia |
| title_short |
Generation of a novel rodent model for DYT1 dystonia |
| title_full |
Generation of a novel rodent model for DYT1 dystonia |
| title_fullStr |
Generation of a novel rodent model for DYT1 dystonia |
| title_full_unstemmed |
Generation of a novel rodent model for DYT1 dystonia |
| title_sort |
generation of a novel rodent model for dyt1 dystonia |
| publisher |
Elsevier |
| series |
Neurobiology of Disease |
| issn |
1095-953X |
| publishDate |
2012-07-01 |
| description |
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. |
| topic |
Transgenic rat model TorsinA DYT1 dystonia Movement disorder |
| url |
http://www.sciencedirect.com/science/article/pii/S0969996112000952 |
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