Different data from different labs: Lessons from studies of gene-environment interaction
Different data from different labs: Lessons from studies of gene-environment interaction
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DOI：
10.1002/neu.10173
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Crabbe, JC
中科院分区：
文献类型：
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作者：
Wahlsten, D;Metten, P;Crabbe, JC
有时人们认为，对小鼠行为进行标准化测试将确保不同实验室得到相似的结果。我们通过在独立实验室中使用相同的设备和测试协议进行行为测试来评估这一假设。八个基因组的小鼠，包括相同数量的雄性和雌性，要么在当地饲养，要么从供应商处运来，然后在三个实验室（纽约州奥尔巴尼；艾伯塔省埃德蒙顿；俄勒冈州波特兰）同时测试六种行为。这些行为包括小盒子中的运动活动、高架十字迷宫、加速旋转杆、可见平台水逃逸、可卡因激活运动活动以及两瓶测试中的乙醇偏好。这项研究的初步报告对常规措施进行了常规分析，揭示了基因型和实验室的强烈影响以及基因型和实验室之间值得注意的相互作用。我们现在报告对附加措施的更详细分析，并以不同方式查看每个测试的数据。无论小鼠是从供应商运来的还是本地饲养的，对六项测试中几乎每一项指标的影响都可以忽略不计，并且对于大多数行为来说，性别差异也不存在或非常小，而遗传效应几乎总是很大。对于运动活动、可卡因激活和高架十字迷宫，分析表明行为的遗传差异对进行测试的实验室有很强的依赖性。另一方面，对于乙醇偏好和水逃逸学习，三个实验室在关键行为指标上获得了基本相同的结果。因此，很明显，结果对特定实验室的强烈依赖性本身也取决于所讨论的任务。我们的结果表明，测试标准化可能有优势，但实验室环境可能永远无法足够相似，以保证在各种实验室的各种测试中获得相同的结果。我们回顾了神经科学领域的同事以及大众媒体对我们结果的解释。媒体中普遍存在但在神经科学家中相对罕见的悲观观点，认为小鼠行为测试非常不可靠，这与我们的数据相矛盾。尽管基因型和实验室环境之间存在值得注意的相互作用，但近交系之间的大部分较大差异在三个实验室中得到了复制。另一方面，中等效应大小的菌株差异通常在实验室之间存在显着差异，尤其是涉及三个 129 衍生菌株的实验室。讨论了小鼠靶向突变和诱导突变行为筛查的意义。 (C) 2003 年 Wiley 期刊公司。
It is sometimes supposed that standardizing tests of mouse behavior will ensure similar results in different laboratories. We evaluated this supposition by conducting behavioral tests with identical apparatus and test protocols in independent laboratories. Eight genetic groups of mice, including equal numbers of males and females, were either bred locally or shipped from the supplier and then tested on six behaviors simultaneously in three laboratories (Albany, NY; Edmonton, AB; Portland, OR). The behaviors included locomotor activity in a small box, the elevated plus maze, accelerating rotarod, visible platform water escape, cocaine activation of locomotor activity, and ethanol preference in a two-bottle test. A preliminary report of this study presented a conventional analysis of conventional measures that revealed strong effects of both genotype and laboratory as well as noteworthy interactions between genotype and laboratory. We now report a more detailed analysis of additional measures and view the data for each test in different ways. Whether mice were shipped from a supplier or bred locally had negligible effects for almost every measure in the six tests, and sex differences were also absent or very small for most behaviors, whereas genetic effects were almost always large. For locomotor activity, cocaine activation, and elevated plus maze, the analysis demonstrated the strong dependence of genetic differences in behavior on the laboratory giving the tests. For ethanol preference and water escape learning, on the other hand, the three labs obtained essentially the same results for key indicators of behavior. Thus, it is clear that the strong dependence of results on the specific laboratory is itself dependent on the task in question. Our results suggest that there may be advantages of test standardization, but laboratory environments probably can never be made sufficiently similar to guarantee identical results on a wide range of tests in a wide range of labs. Interpretations of our results by colleagues in neuroscience as well as the mass media are reviewed. Pessimistic views, prevalent in the media but relatively uncommon among neuroscientists, of mouse behavioral tests as being highly unreliable are contradicted by our data. Despite the presence of noteworthy interactions between genotype and lab environment, most of the larger differences between inbred strains were replicated across the three labs. Strain differences of moderate effects size, on the other hand, often differed markedly among labs, especially those involving three 129-derived strains. Implications for behavioral screening of targeted and induced mutations in mice are discussed. (C) 2003 Wiley Periodicals, Inc.