抑郁和抗抑郁表型的基因工程小鼠模型

doi:10.3969/j.issn.1674-5817.2015.02.012

摘要/Abstract

摘要： 抑郁和抗抑郁表型的基因敲除小鼠、敲减小鼠的发展利于更好地理解基因、环境和后天因素在抑郁症发生中的作用与关系。5-羟色胺(5-HT)神经传递的功能障碍是抑郁症共同的标志,利用基因工程技术对5-HT系统中重要的转运体、受体、蛋白、酶等基因进行敲除或敲减制成的基因工程小鼠模型具有抑郁和抗抑郁表型。文章综述了十种有代表性的基因工程小鼠模型(5种抑郁表型、5种抗抑郁表型),分别从其生理功能、分子机制、行为学表型、神经生理学改变乃至这些基因所对应的人体层面的研究进行了总结,而人体层面研究的发现有助于设计和建立新的基因小鼠模型,用于探索新的抑郁症的发病假说,从而为探索新的抗抑郁药物提供依据。

关键词: 抑郁, 抗抑郁, 行为学表型, 5-羟色胺(5-HT), 基因工程, 小鼠模型

Abstract: The development of knockout or knockdown mice, showing a depressive or depression-resistant phenotype, have allowed us to better understand the complex relationship between genes, behavior and acquired disposition in mood disorders. Preclinical and clinical studies have established that a dysfunction of serotonin (5-HT) neurotransmission is a common hallmark in depression. Genetic mice models with a gene manipulation of?transporter, receptor, protein, enzyme gene in 5-HT system show depressive or depression-resistant phenotype. The present review revises ten genetically engineered mice models with mood alteration (either includes 5 genotypes) and summarizes their each physiological fuction,molecular mechanism, behavioristics,neurophysiology and even those translated to human. In turn, findings from human studies have helped to design and generate genetic mice models to explore new hypothesis of the etiology of human depression, and most important, to explore and refine new strategies for antidepressant medication.

Key words: Depression, Depression-resistance, Behavioral phenotype, Serotonin, Genetic Engineering, Mice models

中图分类号:

Q95-33

王晓洁, 张志珺, 叶冬青. 抑郁和抗抑郁表型的基因工程小鼠模型[J]. 实验动物与比较医学, 2015, 35(2): 142-148.

WANG Xiao-jie, ZHANG Zhi-jun, YE Dong-qing. Genetic Engineering Mice Models of Depressive-like or Depression-resistant Phenotype[J]. Laboratory Animal and Comparative Medicine, 2015, 35(2): 142-148.

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