Abstract
The DYT1 gene containing a trinucleotide deletion (DeltaGAG) is linked to early-onset dystonia, a neurological movement disorder of involuntary muscle contractions. To understand DYT1's contribution to dystonia, we produced and analyzed Dyt1 knockdown (KD) mice that expressed a reduced level of torsinA protein encoded by Dyt1. Knockdown mice exhibited deficits in motor control and a decreased trend in dopamine with a significant reduction in 3,4-dihydroxyphenylacetic acid. These alterations are similar to those displayed by previously reported Dyt1 DeltaGAG knockin heterozygous mice, suggesting that the partial loss of torsinA function contributes to the pathology of the disease.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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3,4-Dihydroxyphenylacetic Acid / metabolism
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Alleles
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Animals
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Blotting, Western
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Dopamine / metabolism
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Exons / genetics
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Genetic Vectors
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Genotype
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Homovanillic Acid
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Hyperkinesis / genetics*
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Hyperkinesis / physiopathology*
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Mice
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Mice, Knockout
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Molecular Chaperones / genetics*
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Molecular Chaperones / physiology*
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Monoamine Oxidase / metabolism
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Motor Activity / physiology
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Neostriatum / metabolism
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Neuromuscular Diseases / genetics*
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Neuromuscular Diseases / physiopathology
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RNA / biosynthesis
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Sex Characteristics
Substances
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Dyt1 protein, mouse
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Molecular Chaperones
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RNA, Messenger
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3,4-Dihydroxyphenylacetic Acid
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RNA
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Monoamine Oxidase
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Dopamine
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Homovanillic Acid