Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests
Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests
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DOI：
10.1016/s0006-8993(98)01258-x
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发表时间：
1999-07-17
期刊：
影响因子：
2.9
通讯作者：
Crawley, JN
中科院分区：
文献类型：
--
作者：
Crawley, JN
严格的实验设计可以最大限度地减少新的转基因或基因敲除小鼠行为表型的假阳性和假阴性的高风险。使用完善的、定量的、可重复的行为任务，适当的n，正确的统计方法，考虑亲本菌株贡献的背景基因，并注意产仔和性别问题，将最大限度地提高-/-、+/-和+/+基因型的有意义的比较。本综述描述了我们实验室开发和使用的策略。初步观察评估一般健康和神经反射。感觉能力和运动功能被广泛量化。具体测试包括观察家庭笼行为、体重、体温、皮毛和胡须的外观、翻正反射、声惊吓、眨眼、瞳孔收缩、触须反射、耳廓反射、Digiscan开阔场地运动、旋转杆运动协调、挂线、足迹路径、视觉悬崖、听觉阈值、疼痛阈值和嗅觉灵敏度。假设检验集中在每个相关行为领域内至少三个经过验证的任务上。本文描述了小鼠在学习和记忆、喂养、伤害感受以及与人类焦虑、抑郁、精神分裂症和药物成瘾等离散症状相关的行为领域的具体测试。我们的方法在C/EBP δ敲除小鼠的行为表型中得到了说明，这些小鼠在一般健康、神经反射、感觉和运动任务以及莫里斯水任务方面表现正常，但在情境恐惧条件反射方面表现出显著增强的表现。(C) 1999 Elsevier Science B.V.版权所有
Rigorous experimental design can minimize the high risk of false positives and false negatives in the behavioral phenotyping of a new transgenic or knockout mouse. Use of well established, quantitative, reproducible behavioral tasks, appropriate Ns, correct statistical methods, consideration of background genes contributed by the parental strains, and attention to litter and gender issues, will maximize meaningful comparisons of -/-, +/-, and +/+ genotypes. Strategies developed and used by our laboratory are described in this review. Preliminary observations evaluate general health and neurological reflexes. Sensory abilities and motor functions are extensively quantitated. Specific tests include observations of home cage behaviors, body weight, body temperature, appearance of the fur and whiskers, righting reflex, acoustic startle, eye blink, pupil constriction, vibrissae reflex, pinna reflex, Digiscan open field locomotion, rotarod motor coordination, hanging wire, footprint pathway, visual cliff, auditory threshold, pain threshold, and olfactory acuity. Hypothesis testing then focuses on at least three well-validated tasks within each relevant behavioral domain. Specific tests for mice are described herein for the domains of learning and memory, feeding, nociception, and behaviors relevant to discrete symptoms of human anxiety, depression, schizophrenia, and drug addiction. An example of our approach is illustrated in the behavioral phenotyping of C/EBP delta knockout mice, which appear to be normal on general health, neurological reflexes, sensory and motor tasks, and the Morris water task, but show remarkably enhanced performance on contextual fear conditioning. (C) 1999 Elsevier Science B.V. All rights reserved.