Mouse Model Of Autistic Repetitive Behavior

自闭症重复行为小鼠模型

• 批准号: 6623490
• 负责人: Joseph Paul Garner
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-10 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6623490
• 关键词: autism; behavior test; behavioral /social science research tag; cognition; compulsive behavior; disease /disorder model; ethology; gamblings; laboratory mouse; model design /development; neuropsychological tests; videotape /videodisc

DESCRIPTION (provided by applicant): The presence of abnormal repetitive behaviors is necessary for a diagnosis of autism. These behaviors can be distressing, self-injurious, and difficult to treat. Despite their importance however, abnormal repetitive behaviors have received far less attention from researchers than other symptoms of autism. The specific goal of this project is therefore to develop an animal model of abnormal repetitive symptoms in autism. Abnormal repetitive behaviors in autistic patients are associated with disruption of 'executive' systems which are responsible for selecting and sequencing behavior. The performance of different executive systems can be measured using distinct neuropsychological tasks. Abnormal repetitive behavior in autism can be divided into 'high-level' behaviors which correlate with impairments in 'high-level' executive systems, measured using the IDED task; and 'low-level' behaviors which correlate with impairments in 'low-level' executive systems, measured using the gambling task. Abnormal repetitive behaviors commonly develop in captive animals. C57BL6/J laboratory mice perform two kinds - barbering (hair-pulling), and stereotypy - that closely resemble 'high-level' and 'low-level' behaviors respectively in autistic patients. If these behaviors are indeed equivalent to autistic symptoms they should correlate with the same measures of executive dysfunction. We will use a number of cognitive tasks, including the IDED and gambling tasks, to measure executive dysfunction in the mice. Our specific aims are therefore to: 1) develop standardized methods for recording these behaviors and performing these tasks in mice; 2) test the prediction that barbering will correlate with impairments on the IDED tasks; and 3) test the prediction that stereotypy will correlate with impairment on the gambling task. Developing a model of these symptoms in mice opens up several exciting new avenues for future research into environmental factors, genetic factors, and possible therapies.

描述(申请人提供)：存在异常重复 行为对于自闭症的诊断是必要的。这些行为可能是 痛苦的，自我伤害的，难以治疗的。尽管它们很重要 然而，反常的重复行为受到的关注却远远少于 研究人员不是自闭症的其他症状。这个项目的具体目标是 因此，建立一种自闭症异常重复症状的动物模型。 自闭症患者的异常重复行为与 扰乱负责选拔和管理的“行政”系统 排序行为。不同执行系统的性能可以是 使用不同的神经心理学任务进行测量。反常重复行为 在自闭症中可以分为与以下因素相关的高水平行为 “高级”执行系统中的损伤，使用IDED任务进行测量； 以及与“低水平”中的损伤相关的“低水平”行为 执行系统，使用赌博任务进行测量。异常重复 行为通常发生在圈养动物身上。C57BL6/J实验室小鼠表现 两种类型--理发(拔头发)和刻板印象--非常相似 自闭症患者的“高水平”和“低水平”行为。如果 这些行为实际上等同于他们应该出现的自闭症症状 与相同的执行功能障碍的衡量标准相关。我们将使用一个数字 认知任务，包括IDED和赌博任务，以测量执行力 小鼠的功能障碍。因此，我们的具体目标是：1)发展 记录这些行为并执行这些任务的标准化方法 在小鼠身上；2)测试理发与损伤相关的预测 以及3)检验刻板印象将与 在赌博任务上有障碍。正在开发这些症状的模型 MICE为未来的研究开辟了几个令人兴奋的新途径 环境因素、遗传因素和可能的治疗方法。

项目成果

Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach.

• DOI: 10.1016/j.bbr.2011.01.002
• 发表时间: 2011-06-01
• 期刊: BEHAVIOURAL BRAIN RESEARCH
• 影响因子: 2.7
• 作者: Garner, Joseph P.;Thogerson, Collette M.;Dufour, Brett D.;Wuerbel, Hanno;Murray, James D.;Mench, Joy A.
• 通讯作者: Mench, Joy A.

Barbering (fur and whisker trimming) by laboratory mice as a model of human trichotillomania and obsessive-compulsive spectrum disorders.

实验室小鼠的理发（毛皮和胡须修剪）作为人类拔毛癖和强迫症谱系障碍的模型。

• 发表时间: 2004
• 期刊: Comparative medicine.
• 作者: Garner,JosephP;Weisker,SandraM;Dufour,Brett;Mench,JoyA
• 通讯作者: Mench,JoyA