The MitoPark mouse--a new model for Parkinson's Disease

MitoPark小鼠——帕金森病的新模型

• 批准号: 7733848
• 负责人: Barry J Hoffer
• 金额: $ 97.41万
• 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/7733848
• 关键词: Adult; Cell Death; Characteristics; Disease; Functional disorder; Knockout Mice; Lewy Bodies; Metabolic; Midbrain structure; Mitochondria; Mitochondrial DNA; Mitochondrial Membrane Protein; Modeling; Mus; Parkinson Disease; Parkinsonian Disorders; Respiratory Chain; Role; Symptoms; alpha synuclein; cell injury; dopamine system; dopaminergic neuron; mitochondrial dysfunction; mitopark mouse; neuropathology; novel; positional cloning

We have used a reverse genetic approach to investigate this question and created conditional knockout mice with reduced mtDNA expression in midbrain DA neurons. These mice have adult onset of slowly progressive, typical parkinsonian symptoms accompanied by progressive formation of intracellular inclusions and characteristic neuropathology. The inclusions are present in most DA neurons and contain both mitochondrial membranes and proteins. Our findings thus support an etiological role for respiratory chain dysfunction Parkinsons disease and suggest a novel mechanism for the formation of Lewy bodies.

我们已经使用了反向遗传学的方法来研究这个问题，并创建了条件性基因敲除小鼠与中脑DA神经元的mtDNA表达减少。 这些小鼠成年后出现缓慢进展的典型帕金森病症状，伴有细胞内包涵体的进展性形成和特征性神经病理学。 内含物存在于大多数DA神经元中，包含线粒体膜和蛋白质。因此，我们的研究结果支持呼吸链功能障碍帕金森病的病因作用，并提出了一种新的机制，形成路易体。