altered dendritic morphology of purkinje cells in dyt1 δgag knock-in and purkinje cell-specific dyt1 conditional knockout mice浦肯野细胞的树突形态改变dyt1δgag敲入和浦肯野特异性dyt1条件基因敲除小鼠.pdfVIP

Altered Dendritic Morphology of Purkinje cells in Dyt1 DGAG Knock-In and Purkinje Cell-Specific Dyt1 Conditional Knockout Mice 1 1 1 1 2 1 Lin Zhang , Fumiaki Yokoi , Yuan-Hu Jin , Mark P. DeAndrade , Kenji Hashimoto , David G. Standaert , Yuqing Li1* 1 Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan Abstract Background: DYT1 early-onset generalized dystonia is a neurological movement disorder characterized by involuntary muscle contractions. It is caused by a trinucleotide deletion of a GAG (DGAG) in the DYT1 (TOR1A) gene encoding torsinA; the mouse homolog of this gene is Dyt1 (Tor1a). Although structural and functional alterations in the cerebellum have been reported in DYT1 dystonia, neuronal morphology has not been examined in vivo. Methodology/Principal Findings: In this study, we examined the morphology of the cerebellum in Dyt1 DGAG knock-in (KI) mice. Golgi staining of the cerebellum revealed a reduction in the length of primary dendrites and a decrease in the number of spines on the distal dendrites of Purkinje cells. To determine if this phenomenon was cell autonomous and mediated by a loss of torsinA function in Purkinje cells, we created a knockout of the Dyt1 gene only in Purkinje cells of mice. We found the Purkinje-cell specific Dyt1 conditional knockout (Dyt1 pKO) mice have similar alterations in Purkinje cell morphology, with shortened primary dendrites and decreased spines on the distal dendrites. Conclusion/Significance: These results suggest