Abstract：
Intellectual disabilities (ID) constitute a class of human neurodevelopmental diseases and are a major medical and socioeconomic problem owing to their high incidence and enormous burden to the families of those affected. In the past three decades, mutant mouse technologies have provided powerful tools for elucidating the pathophysiological mechanisms underlying behavioral and developmental alterations related to IDs and for addressing new therapeutic strategies, and major progress has been made revealing previously unidentified genes involved in ID. However, the pathological hallmarks of IDs are very heterogeneous in regard to both the functional deficits observed and the severity of the phenotype, even within the same mutation types. For this reason, an appropriate experimental design is required to reduce the risk of false negatives and positives in animal functional genomic studies. This experimental design should address functions important to evaluate, tests, and the appropriate workflow. Here, we propose an extensive behavioral screen with detailed protocols, which was successfully used in a systematic mouse functional genomic approach to gain pathway-based insights into mechanisms leading to cognitive dysfunction in humans. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Assessment of circadian activity and ingestive behavior Basic Protocol 2: Assessment of neurological reflexes and motor abilities using the grip and rotarod tests Basic Protocol 3: Evaluation of anxiety-related behavior using the elevated plus maze Basic Protocol 4: Evaluation of recognition memory using the object recognition task Basic Protocol 5: Evaluation of social behavior using the social recognition test Basic Protocol 6: Evaluation of working memory using the Y-maze spontaneous alternation test Basic Protocol 7: Evaluation of emotional learning and memory using the fear conditioning test.
摘要：
智力障碍（ID）是一类人类神经发育疾病，是一个重大的医学和社会经济问题，因为它们的发病率很高，给受影响者的家庭带来了巨大的负担。在过去的三十年里，突变小鼠技术为阐明与ID相关的行为和发育改变的病理生理机制以及解决新的治疗策略提供了强大的工具，并且已经取得了重大进展，揭示了以前未知的与ID有关的基因。然而,ID的病理标志在观察到的功能缺陷和表型的严重程度方面是非常异质的，即使在相同的突变类型内。出于这个原因,在动物功能基因组研究中，需要适当的实验设计来降低假阴性和阳性的风险。此实验设计应解决对评估重要的功能，测试,和适当的工作流程。这里,我们提出了一个带有详细协议的广泛行为屏幕，该方法已成功用于系统的小鼠功能基因组方法，以获得对导致人类认知功能障碍的机制的基于途径的见解。©2022Wiley期刊有限责任公司。基本方案1：昼夜节律活动和摄食行为的评估基本方案2：使用握力和旋转杆测试评估神经反射和运动能力基本方案3：使用高架迷宫评估与焦虑相关的行为基本方案4：使用对象识别任务评估识别记忆基本方案5：使用社会识别测试评估社会行为基本方案6：使用Y迷宫交替评估工作记忆基本方案7：使用情感学习条件评估。
