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In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice.
寻找抑郁小鼠: 研究转基因小鼠抑郁相关行为模型的效用。

摘要

The ability to modify mice genetically has been one of the major breakthroughs in modern medical science affecting every discipline including psychiatry. It is hoped that the application of such technologies will result in the identification of novel targets for the treatment of diseases such as depression and to gain a better understanding of the molecular pathophysiological mechanisms that are regulated by current clinically effective antidepressant medications. The advent of these tools has resulted in the need to adopt, refine and develop mouse-specific models for analyses of depression-like behavior or behavioral patterns modulated by antidepressants. In this review, we will focus on the utility of current models (eg forced swim test, tail suspension test, olfactory bulbectomy, learned helplessness, chronic mild stress, drug-withdrawal-induced anhedonia) and research strategies aimed at investigating novel targets relevant to depression in the mouse. We will focus on key questions that are considered relevant for examining the utility of such models. Further, we describe other avenues of research that may give clues as to whether indeed a genetically modified animal has alterations relevant to clinical depression. We suggest that it is prudent and most appropriate to use convergent tests that draw on different antidepressant-related endophenotypes, and complimentary physiological analyses in order to provide a program of information concerning whether a given phenotype is functionally relevant to depression-related pathology.

译文

基因改造老鼠的能力是现代医学的重大突破之一,它影响着包括精神病学在内的每一门学科。人们希望这些技术的应用将导致识别治疗抑郁症等疾病的新靶点,并更好地理解由目前临床有效的抗抑郁药物。这些工具的出现导致了采用、完善和开发老鼠特异性模型的需要,这些模型用于分析抗抑郁药调节的抑郁样行为或行为模式。在这篇综述中,我们将重点关注当前模型的效用 (如强迫游泳试验、尾部悬吊试验、嗅球切除术、习得性无助、慢性轻度压力、戒毒引起的快感缺乏) 以及旨在研究小鼠抑郁症相关的新靶点的研究策略。我们将重点关注被认为与检查此类模型的效用相关的关键问题。此外,我们描述了其他可能提供线索的研究途径,即转基因动物是否确实具有与临床抑郁症相关的改变。我们建议使用聚合测试借鉴不同的抗抑郁相关内表型是谨慎且最合适的, 以及免费的生理分析,以便提供一个关于给定表型是否与抑郁症相关病理功能相关的信息程序。

genetically modified mice

肿瘤 转基因 动物模型
概述  :  

转基因小鼠是指染色体基因组中整合有外源基因并能表达的稳定遗传的小鼠。转基因技术则是指制备转基因动物所需的一套技术,它涉及外源基因的构建、载体和受体的筛选、基因导人技术、供转基因胚胎发育的体外培养系统和宿主动物等许多方面。   1974年,Jaenish和Mintz应用显微注射法,在世界上首次成功地获得了SV40 DNA转基因小鼠。1980年,Gordon等人首先育成带有人胸腺激酶基因的转基因小鼠,尤其是1982年Palmiter等人将大鼠的生长

Genetically   英 /dʒəˈnetɪkli/   美 /dʒə'nɛtɪklɪ/

释    义   adv. 从遗传学角度;从基因方面

例    句   These attributes are genetically programmed functions of normal cells that are intended to combat infection or repair injury. 这些属性是正常细胞的基因编程功能,此举的目的是抗击感染或修复损伤。

 

Modified   英 /ˈmɒdɪfaɪd/   美 /mɑdəˌfaɪd/

释    义   adj. 改进的,修改的;改良的

               v. 修改;缓和(modify的过去分词)

同根词   modifiable adj. 可修饰的;可更改的

               modification n. 修改,修正;改变

               modify vi. 修改

               modify vt. 修改,修饰;更改

例    句   Its systems move virtual models of prototype machinery and products around manufacturing plants to determine how existing equipment would have to be moved or modified. 该系统将原型机械与产品的虚拟模型在制造厂内到处移动,以决定现有的设备需要怎样的移动或改进。

 

Mice   英 /maɪs/   美 /maɪs/

释    义   n. 老鼠(mouse的复数)

例    句   So Tsai decided to see if they would have any effect on her mice with damaged brain cells.所以蔡决定看看它们是否会对她的脑细胞受损的老鼠有任何影响。

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