MOUSE SYNAPTIC VESICULAR MONAMINE TRANSPORTER

小鼠突触囊泡单胺转运蛋白

• 批准号: 6289591
• 负责人: George Richard Uhl
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6289591
• 关键词: amphetamines; animal genetic material tag; complementary DNA; dopamine; dopamine transporter; embryonic stem cell; gene deletion mutation; genetic regulatory element; laboratory mouse; methylphenyltetrahydropyridine; molecular cloning; neurotoxicology; neurotoxins; neurotransmitter transport; nucleic acid sequence; synaptic vesicles; transcription factor; transfection /expression vector

Activities of the principal brain vesicular monamine transporter, VMAT2, are key to understanding the cellular compartmentalization of monoamines that may play a key role in modulating the actions and neurotoxicities induced by amphetamine and by each of the toxins that selectively kills dopaminergic neurons to provide the best current models of Parkinsons disease. In this year, workers in this Branch continued to describ the properties of knockout mice with deletions of the VMAT2 gene. EKG monitoring revealed a good correlation betwen the sudden death experiences by some VMAT2 deficient heterozygote mice and prolonged QT intervals. Aging studies documented clear reductions in locomotion and in amphetamine responsiveness. Mice with deletions of VMAT2 and the plasma membrane transporters DAT and SERT are viable and fertile. VMAT2 knockout mice continue to substantially enhance our understanding of mechanisms of age interactions with psychostimulants, locomotor systems and mechanisms apparently predisposing to fatal cardiac arrythmias. - amphetamine Parkinson's disease Age Cardiac arrythmias - Human Subjects: Interview, Questionaires, or Surveys Only

主要脑囊泡单胺转运蛋白 VMAT2 的活性是了解单胺细胞区室化的关键，单胺可能在调节安非他明和选择性杀死多巴胺能神经元的每种毒素诱导的作用和神经毒性方面发挥关键作用，以提供最佳的治疗效果。目前的帕金森病模型。今年，该部门的工作人员继续描述删除了VMAT2基因的基因敲除小鼠的特性。心电图监测显示，一些 VMAT2 缺陷杂合子小鼠的猝死经历与 QT 间期延长之间存在良好的相关性。衰老研究记录了运动能力和安非他明反应能力明显下降。缺失 VMAT2 以及质膜转运蛋白 DAT 和 SERT 的小鼠具有存活能力和生育能力。 VMAT2 敲除小鼠继续大大增强我们对年龄与精神兴奋剂、运动系统和明显易导致致命心律失常的机制的相互作用机制的理解。 - 安非他明 帕金森病 年龄 心律失常 - 人类受试者：仅限访谈、问卷或调查