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）：进行性核上麻痹（PSP）属于一种称为“ tauopanties”的神经退行性疾病家族，并且是最常见的非典型神经退行性帕金森氏症疾病，其估计患病率为4-6.5/ 100,000。该疾病的症状通常出现在50至80岁之间，包括姿势不稳定，近视垂直视线麻痹，严重的言语和吞咽困难以及情绪和行为的改变。症状发作后的几年内，该疾病逐渐使人衰弱，患者在几年内死亡。迄今为止，尚无PSP的治疗方法，开发疾病的疗法需要进一步了解与PSP相关的神经病理学变化的机制。因此，概括该疾病表型特征的小鼠模型将是了解疾病过程并测试新的治疗策略的宝贵工具。这种鼠标模型尚未建立。该应用程序的主要目标是生成PSP的鼠标模型。 小鼠模型在PSP中的可用性不仅可以进一步理解对tauopathies中发生的神经病理学变化，而且还可以为这种毁灭性疾病开发新的治疗干预措施。 公共卫生相关性：进行性核上麻痹（PSP）属于一个称为“ tauopathies”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氏病。症状出现几年后，这种疾病不可避免地致命，死亡发生。对这种疾病的小鼠模型的产生和分析将为PSP和其他功提供的潜在新治疗干预措施提供见解。