Crawley J N
Section on Behavioral Neuropharmacology, Experimental Therapeutics Branch, National Institute of Mental Health, Building 10, Room 4D11, Bethesda, MD 20892-1375, USA.
Brain Res. 1999 Jul 17;835(1):18-26. doi: 10.1016/s0006-8993(98)01258-x.
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/EBPdelta 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.
严谨的实验设计可以将新的转基因或基因敲除小鼠行为表型分析中出现假阳性和假阴性的高风险降至最低。使用成熟的、定量的、可重复的行为任务、合适的样本量、正确的统计方法、考虑亲本品系贡献的背景基因以及关注窝仔和性别问题，将最大限度地实现对 -/ -、+ / - 和 + / + 基因型进行有意义的比较。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状况和神经反射。对感觉能力和运动功能进行广泛定量。具体测试包括观察笼内行为、体重、体温、皮毛和胡须外观、翻正反射、听觉惊吓、眨眼、瞳孔收缩、触须反射、耳廓反射、Digiscan旷场运动、转棒运动协调、悬线、足迹路径、视觉悬崖、听觉阈值、疼痛阈值和嗅觉敏锐度。然后，假设检验聚焦于每个相关行为领域内至少三项经过充分验证的任务。本文针对学习与记忆、进食、伤害感受以及与人类焦虑、抑郁、精神分裂症和药物成瘾的离散症状相关的行为等领域，描述了针对小鼠的具体测试。我们方法的一个例子体现在C/EBPδ基因敲除小鼠的行为表型分析中，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迷宫任务中似乎正常，但在情境恐惧条件反射中表现出显著增强的能力。
