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• W1982736767 abstract "A single GAG deletion in Exon 5 of the TOR1A gene is associated with a form of early-onset primary dystonia showing less than 40% penetrance. To provide a framework for cellular and systems study of DYT1 dystonia, we characterized the genetic, behavioral, morphological and neurochemical features of transgenic mice expressing either human wild-type torsinA (hWT) or mutant torsinA (hMT1 and hMT2) and their wild-type (WT) littermates. Relative to human brain, hMT1 mice showed robust neural expression of human torsinA transcript (3.90×). In comparison with WT littermates, hMT1 mice had prolonged traversal times on both square and round raised-beam tasks and more slips on the round raised-beam task. Although there were no effects of genotype on rotarod performance and rope climbing, hMT1 mice exhibited increased hind-base widths in comparison to WT and hWT mice. In contrast to several other mouse models of DYT1 dystonia, we were unable to identify either torsinA- and ubiquitin-positive cytoplasmic inclusion bodies or nuclear bleb formation in hMT1 mice. High-performance liquid chromatography with electrochemical detection was used to determine cerebral cortical, striatal, and cerebellar levels of dopamine (DA), norepinephrine, epinephrine, serotonin, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid. Although there were no differences in striatal DA levels between WT and hMT1 mice, DOPAC and HVA concentrations and DA turnover (DOPAC/DA and HVA/DA) were significantly higher in the mutants. Our findings in DYT1 transgenic mice are compatible with previous neuroimaging and postmortem neurochemical studies of human DYT1 dystonia. Increased striatal dopamine turnover in hMT1 mice suggests that the nigrostriatal pathway may be a site of functional neuropathology in DYT1 dystonia." @default.
• W1982736767 created "2016-06-24" @default.
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• W1982736767 date "2008-04-01" @default.
• W1982736767 modified "2023-10-12" @default.
• W1982736767 title "Abnormal motor function and dopamine neurotransmission in DYT1 ΔGAG transgenic mice" @default.
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• W1982736767 doi "https://doi.org/10.1016/j.expneurol.2007.12.027" @default.
• W1982736767 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2390904" @default.
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