恒河猴和食蟹猴脑疾病模型的标准化日常行为采集和分析系统的建立及其在孤独症谱系障碍中的应用

任晓峰; 王慧敏; 吕小满; 周仪; 范颖尹; 余妍君; Christoph W. TURCK; 陈雨慧; 吕龙宝; 胡英周; 李浩; 王文超; 秦冬冬; 冯晓丽; 胡新天

doi:10.1631/jzus.B2400294

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恒河猴和食蟹猴脑疾病模型的标准化日常行为采集和分析系统的建立及其在孤独症谱系障碍中的应用

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Research Article | Updated：2024-12-03

恒河猴和食蟹猴脑疾病模型的标准化日常行为采集和分析系统的建立及其在孤独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
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2024年25卷第11期页码：972-995
Affiliations：

1.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, Kunming650107, China
2.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, Kunming650201, China
3.Department of Physiology, Faculty of Basic Medical Science, Kunming Medical University, Kunming650500, China
4.Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Neuropsychiatric Diseases, Yunnan University of Chinese Medicine, Kunming650500, China
5.University of Chinese Academy of Sciences, Beijing101408, China
Funds：

the Key-Area Research and Development Program of Guangdong Province(2019B030335001);the STI2030-Major Projects(2021ZD0200900);the National Key Research and Development Program of China(2021YFF0702700;2018YFA0801403);the National Natural Science Foundation of China(81960422;32100801;82101241;82360226;82160923;82260929;82374425;32460194);the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)(XDB32060200);the STI2030-Major Projects(2022ZD0205200;2022ZD0212700);the Science and Technology Department of Yunnan Province(202305AH340006;202305AH340007);the Yunnan Fundamental Research Projects(202201AT070153;202201AT070139);the Science and Technology Project of Yunnan Province(202101AY070001-001);the Yunnan Revitalization Talent Support Program(YNWR-QNBJ-2019-043);the CAS “Light of West China” Program, and the Yunnan Revitalization Talents Support Plan
DOI：10.1631/jzus.B2400294
中图分类号：
CSTR：
纸质出版日期： 2024-11-15 ，

收稿日期： 2024-06-06 ，

修回日期： 2024-09-25 ，
Accepted：

任晓峰,王慧敏,吕小满等.恒河猴和食蟹猴脑疾病模型的标准化日常行为采集和分析系统的建立及其在孤独症谱系障碍中的应用[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(11):972-995.

XIAOFENG REN, HUIMIN WANG, XIAOMAN LV, et al. 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. [J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2024, 25(11): 972-995.
任晓峰,王慧敏,吕小满等.恒河猴和食蟹猴脑疾病模型的标准化日常行为采集和分析系统的建立及其在孤独症谱系障碍中的应用[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(11):972-995. DOI： 10.1631/jzus.B2400294.

XIAOFENG REN, HUIMIN WANG, XIAOMAN LV, et al. 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. [J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2024, 25(11): 972-995. DOI： 10.1631/jzus.B2400294.

摘要

复杂脑疾病严重危害人类健康，目前缺乏早期诊断生物标志物和有效的治疗方法。由于人类研究受到伦理的限制，猴模型的建立对解决这些问题至关重要。随着转基因技术的快速发展，一系列脑疾病，尤其是孤独症谱系障碍（ASD）的转基因猴模型已被成功建立。然而，要建立实用、有效的脑疾病模型，并将其应用于疾病机理和治疗研究中，目前还缺乏一个标准的工具，即脑疾病模型猴的日常行为采集和分析系统。因此，我们以行为表型的全面、定量研究为目标，针对模型构建中常用的恒河猴和食蟹猴，建立了一个标准的日常行为采集和分析系统，包括行为数据采集方法和猴日常行为目录（MDBE）。然后，我们以ASD为应用实例，参考广泛用于临床疾病和模型研究的《精神障碍诊断与统计手册》（第五版，修订版）（DSM-5-TR）中的ASD核心临床症状，基于MDBE建立了一个用于ASD猴模型核心临床症状定量评估的子行为目录（ASD猴核心行为目录（MCBE-ASD））。随后，我们通过实验数据证明了该系统的高度可重复性，并比较了不同恒河猴个体间行为模式的差异。

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.

关键词

猴日常行为目录猴行为采集方法恒河猴食蟹猴孤独症谱系障碍（ASD）

Keywords

Monkey daily behavior ethogramMonkey behavior collection protocolRhesus monkeyCynomolgus monkeyAutism spectrum disorder (ASD)

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