Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study
Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study
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DOI：
10.1152/physiolgenomics.90207.2008
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发表时间：
2008-08-01
影响因子：
4.6
通讯作者：
Wurst, Wolfgang
中科院分区：
文献类型：
--
作者：
Mandillo, Silvia;Tucci, Valter;Wurst, Wolfgang
曼迪洛S，图奇V，霍尔特SM，梅齐亚内H，阿尔·班查阿布奇M，卡尔尼克M，拉德HV，诺兰PM，瓦加扎尔A - M，科吉尔EL，盖尔K，戈利尼E，雅凯S，克雷泽尔W，帕克A，里特F，施耐德I，马拉齐蒂D，奥韦克斯J，布朗SD，尚邦P，罗森塔尔N，托基尼 - 瓦伦蒂尼G，武斯特W。小鼠行为表型分析的可靠性、稳健性和可重复性：一项跨实验室研究。《生理基因组学》34：243 - 255，2008年。首次发表于2008年5月27日；doi:10.1152/physiolgenomics.90207.2008。——建立标准操作程序（SOPs）作为行为表型分析的工具对小鼠功能基因组学至关重要。所设计的测试必须能对所研究的过程提供可靠的测量方法，但最重要的是这些方法在不同时间和实验室之间都具有可重复性。出于这个原因，我们设计并测试了一套SOPs来研究小鼠行为。作为EUMORPHIA项目的一部分，法国、德国、意大利和英国的五个研究中心参与了这项研究。所有程序都经过了一项交叉验证实验研究，以考察所设计方案的稳健性。对四种近交参考品系（C57BL/6J、C3HeB/FeJ、BALB/cByJ、129S2/SvPas）进行了分析以验证这些测试，这四种品系反映了它们在诱变计划中作为常见背景品系的用途。我们证明，所采用的操作程序，包括旷场实验、SHIRPA、握力、转棒、Y迷宫、听觉惊跳反应的前脉冲抑制以及甩尾测试，在多个测试输出参数方面在实验室之间产生了可重复的结果。然而，我们也确定了几个不受控制的变量，这些变量是行为表型分析中的混杂因素。这里所描述的EUMORPHIA SOPs是不断发展日益稳健的表型分析平台及其在大规模、多中心小鼠表型分析项目中应用的一个重要起点。
Mandillo S, Tucci V, Holter SM, Meziane H, Al Banchaabouchi M, Kallnik M, Lad HV, Nolan PM, Ouagazzal A-M, Coghill EL, Gale K, Golini E, Jacquot S, Krezel W, Parker A, Riet F, Schneider I, Marazziti D, Auwerx J, Brown SD, Chambon P, Rosenthal N, Tocchini-Valentini G, Wurst W. Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study. Physiol Genomics 34: 243-255, 2008. First published May 27, 2008; doi:10.1152/physiolgenomics.90207.2008.-Establishing standard operating procedures (SOPs) as tools for the analysis of behavioral phenotypes is fundamental to mouse functional genomics. It is essential that the tests designed provide reliable measures of the process under investigation but most importantly that these are reproducible across both time and laboratories. For this reason, we devised and tested a set of SOPs to investigate mouse behavior. Five research centers were involved across France, Germany, Italy, and the UK in this study, as part of the EUMORPHIA program. All the procedures underwent a cross-validation experimental study to investigate the robustness of the designed protocols. Four inbred reference strains ( C57BL/6J, C3HeB/FeJ, BALB/cByJ, 129S2/SvPas), reflecting their use as common background strains in mutagenesis programs, were analyzed to validate these tests. We demonstrate that the operating procedures employed, which includes open field, SHIRPA, grip-strength, rotarod, Y-maze, prepulse inhibition of acoustic startle response, and tail flick tests, generated reproducible results between laboratories for a number of the test output parameters. However, we also identified several uncontrolled variables that constitute confounding factors in behavioral phenotyping. The EUMORPHIA SOPs described here are an important start-point for the ongoing development of increasingly robust phenotyping platforms and their application in large-scale, multicentre mouse phenotyping programs.