Transgenic mouse model of early-onset DYT1 dystonia
| Autor: | T. Sreenath, Ruth H. Walker, C. W. Olanow, Donald J. Weisz, Ioanna A. Armata, P. Shashidharan, Daniela Sandu, Mitchell F. Brin, U. Potla, Kevin St. P. McNaught |
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| Rok vydání: | 2004 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Transgene Molecular Sequence Data Enolase Mice Transgenic Biology Mice Neurochemical Internal medicine Genetics medicine Animals Humans Amino Acid Sequence Promoter Regions Genetic Molecular Biology Genetics (clinical) Sequence Deletion Dystonia Mental Disorders General Medicine Anatomy medicine.disease Abnormal involuntary movement Endocrinology Gene Expression Regulation Phosphopyruvate Hydratase medicine.symptom Hyperkinesia Lamin Molecular Chaperones Muscle Contraction |
| Zdroj: | Human Molecular Genetics. 14:125-133 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddi012 |
| Popis: | Early-onset dystonia is an autosomal dominant movement disorder associated with deletion of a glutamic acid residue in torsinA. We generated four independent lines of transgenic mice by overexpressing human DeltaE-torsinA using a neuron specific enolase promoter. The transgenic mice developed abnormal involuntary movements with dystonic-appearing, self-clasping of limbs, as early as 3 weeks after birth. Animals also showed hyperkinesia and rapid bi-directional circling. Approximately 40% of transgenic mice from each line demonstrated these severe behavioral abnormalities. Neurochemical analyses revealed decreases in striatal dopamine in affected transgenic mice, although levels were increased in those that had no behavioral changes. Immunohistochemistry demonstrated perinuclear inclusions and aggregates that stained positively for ubiquitin, torsinA and lamin, a marker of the nuclear envelope. Inclusions were detected in neurons of the pedunculopontine nucleus and in other brain stem regions in a pattern similar to what has been described in DYT1 patients. This transgenic mouse model demonstrates behavioral and pathologic features similar to patients with early-onset dystonia and may help to better understand the pathophysiology of this disorder and to develop more effective therapies. |
| Databáze: | OpenAIRE |
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