Generation of a mouse model for Progressive Supranuclear Palsy

进行性核上性麻痹小鼠模型的生成

• 批准号: 8189541
• 负责人: IOANNIS DRAGATSIS
• 金额: $ 7.48万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8189541
• 关键词: A Mouse; Age-Years; Alternative Therapies; Autopsy; Behavior; Cessation of life; Clinical; Communities; Deglutition; Development; Diagnosis; Disease; Family; Gene Mutation; General Population; Generations; Goals; Modeling; Moods; Mutant Strains Mice; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Parkinsonian Disorders; Patients; Prevalence; Process; Progressive Supranuclear Palsy; Speech; Symptoms; Tauopathies; Testing; Therapeutic; Transgenic Organisms; early onset; gaze palsy; insight; meetings; mouse model; novel therapeutic intervention; novel therapeutics; tau aggregation; tau function; therapy development; tool

DESCRIPTION (provided by applicant): Progressive Supranuclear Palsy (PSP) belongs to a family of neurodegenerative disorders referred to as "tauopathies", and is the most frequent atypical neurodegenerative parkinsonian disorder, with an estimated prevalence of 4-6.5/ 100,000 in the general population. Symptoms of the disease usually appear between 50- 80 years of age, and include postural instability, supranuclear vertical gaze palsy, severe speech and swallowing difficulties, and alterations in mood and behavior. The disease is progressively debilitating and patients die within a few years after the onset of symptoms. To date there is no cure for PSP, and development of therapies for the disease require further understanding of the mechanisms underlying the neuropathological changes associated with PSP. A mouse model recapitulating the phenotypic features of the disease would therefore be an invaluable tool to understand the disease process and test new therapeutic strategies. Such mouse model has not been established yet. The main goal of this application is to generate a mouse model for PSP. The availability of a mouse model for PSP will allow not only further understanding of neuropathological changes that occur in tauopathies, but also the possibility of developing new therapeutic interventions for this devastating disorder. PUBLIC HEALTH RELEVANCE: Progressive Supranuclear Palsy (PSP) belongs to a family of neurodegenerative disorders called "tauopathies" and is the most frequent atypical neurodegenerative Parkinsonian disorder. The disease is inevitably fatal with death occurring a few years after symptoms appear. Generation and analyses of a mouse model for this disorder will provide insights for potential new therapeutic interventions for PSP and for other tauopathies.

描述（由申请人提供）：进行性核上性麻痹（PSP）属于被称为“tau蛋白病”的神经退行性疾病家族，是最常见的非典型神经退行性帕金森病，一般估计患病率为 4-6.5/100,000人口。该疾病的症状通常出现在 50-80 岁之间，包括姿势不稳定、核上垂直凝视麻痹、严重言语和吞咽困难以及情绪和行为改变。这种疾病会逐渐使人衰弱，患者在出现症状后几年内就会死亡。迄今为止，PSP 尚无治愈方法，该疾病的治疗方法的开发需要进一步了解与 PSP 相关的神经病理变化的机制。因此，重现疾病表型特征的小鼠模型将成为了解疾病过程和测试新治疗策略的宝贵工具。这种小鼠模型尚未建立。该应用程序的主要目标是为 PSP 生成鼠标模型。 PSP 小鼠模型的出现不仅可以进一步了解 tau 蛋白病中发生的神经病理变化，而且还可以为这种破坏性疾病开发新的治疗干预措施。 公众健康相关性：进行性核上性麻痹 (PSP) 属于称为“tau蛋白病”的神经退行性疾病家族，是最常见的非典型神经退行性帕金森病。这种疾病不可避免地致命，症状出现几年后就会死亡。这种疾病的小鼠模型的生成和分析将为 PSP 和其他 tau蛋白病的潜在新治疗干预提供见解。