Generation of a mouse model for Progressive Supranuclear Palsy

描述(申请人提供)：进行性核上性瘫痪(PSP)属于神经退行性疾病家族，被称为tauopathies，是最常见的非典型神经退行性帕金森病，估计在普通人群中的患病率为4-6.5/100,000。这种疾病的症状通常出现在50-80岁之间，包括姿势不稳定，核上性垂直凝视麻痹，严重的言语和吞咽困难，以及情绪和行为的改变。这种疾病正在逐渐使人虚弱，患者在出现症状后几年内死亡。到目前为止，PSP还没有治愈的方法，这种疾病的治疗方法的发展需要进一步了解与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是了解疾病过程和测试新的治疗策略的宝贵工具。这样的小鼠模型尚未建立。这个应用程序的主要目标是为PSP生成一个鼠标模型。PSP小鼠模型的可获得性不仅将使我们能够进一步了解这种疾病中发生的神经病理变化，而且还可能为这种毁灭性的疾病开发新的治疗干预措施。 公共卫生相关性：进行性核上性瘫痪(PSP)属于神经退行性疾病家族，称为“tauopathies”，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是致命的，死亡发生在症状出现几年后。这种疾病的小鼠模型的建立和分析将为PSP和其他tauopathy的潜在新的治疗干预措施提供见解。

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.