Mouse model of rare TOR1A variant found in sporadic focal dystonia impairs domains affected in DYT1 dystonia patients and animal models

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The GAG deletion in Tor1A (DYT1) is a rare cause of complex musician's dystonia.

Focal dystonia is the most common form of primary dystonia characterized by involuntary twisting, abnormal postures and repetitive movements in a specific body part. Musician’s dystonia (MD) is a type of focal task-specific dystonia that presents with loss of voluntary motor control of extensively trained movements when a musician is playing his instrument. The pathophysiology of focal dystonia...

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Pre-Synaptic Release Deficits in a DYT1 Dystonia Mouse Model

DYT1 early-onset generalized torsion dystonia (DYT1 dystonia) is an inherited movement disorder caused by mutations in one allele of DYT1 (TOR1A), coding for torsinA. The most common mutation is a trinucleotide deletion (ΔGAG), which causes a deletion of a glutamic acid residue (ΔE) in the C-terminal region of torsinA. Although recent studies using cultured cells suggest that torsinA contribute...

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Transgenic mouse model of early-onset DYT1 dystonia.

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 aft...

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The TOR1A (DYT1) gene family and its role in early onset torsion dystonia.

Most cases of early onset torsion dystonia are caused by a 3-bp deletion (GAG) in the coding region of the TOR1A gene (alias DYT1, DQ2), resulting in loss of a glutamic acid in the carboxy terminal of the encoded protein, torsin A. TOR1A and its homologue TOR1B (alias DQ1) are located adjacent to each other on human chromosome 9q34. Both genes comprise five similar exons; each gene spans a 10-k...

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Learning-based animal models: task-specific focal hand dystonia.

Dystonia is a disabling, involuntary disorder of movement that leads to writhing, twisting end-range movements or abnormal postures. Inadequate inhibition could account for excessive excitation and near synchronous co-contractions of agonists and antagonists. Dystonia may be generalized or specific, affecting only one part of the body or involving only a well-learned task (e.g., writing, keyboa...

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ژورنال

عنوان ژورنال: Neurobiology of Disease

سال: 2016

ISSN: 0969-9961

DOI: 10.1016/j.nbd.2016.05.003