motor deficits and decreased striatal dopamine receptor 2 binding activity in the striatum-specific dyt1 conditional knockout mice电动机赤字和减少纹状体多巴胺受体2绑定活动striatum-specific dyt1条件基因敲除小鼠.pdfVIP

Motor Deficits and Decreased Striatal Dopamine Receptor 2 Binding Activity in the Striatum-Specific Dyt1 Conditional Knockout Mice 1 2 3 4 1 Fumiaki Yokoi , Mai Tu Dang , Jianyong Li , David G. Standaert , Yuqing Li * 1 Department of Neurology, College of Medicine, University of Florida, Gainesville, Florida, United States of America, 2 The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America, 3 Department of Biochemistry, Virginia Tech, Blacksburg, Virginia, United States of America, 4 Department of Neurology, School of Medicine, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America Abstract DYT1 early-onset generalized dystonia is a hyperkinetic movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Recently, significant progress has been made in studying pathophysiology of DYT1 dystonia using targeted mouse models. Dyt1 DGAG heterozygous knock-in (KI) and Dyt1 knock-down (KD) mice exhibit motor deficits and alterations of striatal dopamine metabolisms, while Dyt1 knockout (KO) and Dyt1 DGAG homozygous KI mice show abnormal nuclear envelopes and neonatal lethality. However, it has not been clear whether motor deficits and striatal abnormality are caused by Dyt1 mutation in the striatum itself or the end results of abnormal signals from other brain regions. To identify the brain region that contributes to these phenotypes, we made a striatum-specific Dyt1 conditional knockout (Dyt1 sKO) mouse. Dyt1 sKO mice exhibited motor deficits and reduced striatal dopamine receptor 2 (D2R) binding activity, whereas they did not