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Effect of Population Heterogenization on the Reproducibility of Mouse Behavior: A Multi-Laboratory Study

机译：种群异质化对小鼠行为可再现性的影响：多实验室研究

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In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions. Here, we examined whether a simple form of heterogenization effectively improves reproducibility of test results in a multi-laboratory situation. Each of six laboratories independently ordered 64 female mice of two inbred strains (C57BL/6NCrl, DBA/2NCrl) and examined them for strain differences in five commonly used behavioral tests under two different experimental designs. In the standardized design, experimental conditions were standardized as much as possible in each laboratory, while they were systematically varied with respect to the animals' test age and cage enrichment in the heterogenized design. Although heterogenization tended to improve reproducibility by increasing within-experiment variation relative to between-experiment variation, the effect was too weak to account for the large variation between laboratories. However, our findings confirm the potential of systematic heterogenization for improving reproducibility of animal experiments and highlight the need for effective and practicable heterogenization strategies.
机译：在动物实验中，传统上对动物，畜牧业和测试程序进行了标准化，以最大程度地提高测试灵敏度并最大程度地减少动物使用，前提是这也将保证可重复性。但是，通过减少实验内部的差异，标准化可以将推断限制在特定的实验条件下。确实，我们最近在小鼠中发现，标准化可能会在行为测试中产生虚假结果，这说明了可重复性差，并且可以通过系统地改变实验条件来进行种群异质化来避免这种情况。在这里，我们研究了简单的异质化形式是否可以有效地提高在多实验室情况下测试结果的可重复性。六个实验室中的每一个都独立订购了两种自交系（C57BL / 6NCrl，DBA / 2NCrl）的64只雌性小鼠，并在两种不同的实验设计下，在五个常用的行为测试中检查了它们的品系差异。在标准化设计中，每个实验室的实验条件都尽可能地标准化，而在异化设计中，根据动物的试验年龄和网箱富集程度对它们进行了系统地改变。尽管异质化倾向于通过增加实验内差异（相对于实验间差异）来提高可重复性，但效果太弱，无法说明实验室之间的较大差异。但是，我们的发现证实了系统异质化对改善动物实验可重复性的潜力，并突出了对有效且可行的异质化策略的需求。

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