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恒河猴和食蟹猴脑疾病模型标准化日常行为收集与分析系统的建立及其在自闭症谱系障碍中的应用

Establishment of a standardized daily behavior collection and analysis system for brain disease models of rhesus and cynomolgus monkeys and its application in autism spectrum disorder.

作者信息

Ren Xiaofeng, Wang Huimin, Lv Xiaoman, Zhou Yi, Fan Yingyin, Yu Yanjun, Turck Christoph W, Chen Yuhui, Lv Longbao, Hu Yingzhou, Li Hao, Wang Wenchao, Qin Dongdong, Feng Xiaoli, Hu Xintian

机构信息

National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, National Resource Center for Non-human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, China.

Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China.

出版信息

J Zhejiang Univ Sci B. 2024 Nov 15;25(11):972-995. doi: 10.1631/jzus.B2400294.

Abstract

Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.

摘要

复杂的脑部疾病严重威胁人类健康,目前缺乏早期诊断生物标志物和有效的治疗方法。由于人体研究存在伦理限制,建立猴子模型对于解决这些问题至关重要。随着技术的快速发展,一系列脑部疾病的转基因猴子模型,尤其是自闭症谱系障碍(ASD)模型已成功建立。然而,要建立实用且有效的脑部疾病模型并将其应用于疾病机制和治疗研究,仍缺乏一种标准工具,即用于收集和分析脑部疾病模型猴子日常行为的系统。因此,为了全面定量研究行为表型,我们建立了一个标准的日常行为收集和分析系统,包括行为数据收集方案以及针对恒河猴和食蟹猴的猴子日常行为图谱(MDBE),这两种猴子是模型构建中最常用的非人灵长类动物。然后,我们以《精神疾病诊断与统计手册(第五版,修订本)》(DSM - 5 - TR)为参考,将ASD作为应用实例,该手册广泛应用于临床疾病诊断以获取ASD的核心临床症状。接着,我们基于MDBE建立了一个专门用于定量评估ASD猴子模型核心临床症状的子图谱(ASD猴子核心行为图谱(MCBE - ASD))。随后,我们证明了该系统具有高重现性。

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