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Physiol. Genomics 34: 243-255, 2008. First published May 27, 2008; doi:10.1152/physiolgenomics.90207.2008
1094-8341/08 $8.00
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Received 2 April 2008; accepted in final form 23 May 2008.
Physiological Genomics 34:243-255 (2008)
1094-8341/08 $8.00 © 2008 American Physiological Society

Call For Papers: Comparative Genomics

Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study

Silvia Mandillo 4,*, Valter Tucci 3,*, Sabine M. Hölter 1,*, Hamid Meziane 2,*, Mumna Al Banchaabouchi 5,*, Magdalena Kallnik 1,*, Heena V. Lad 3,*, Patrick M. Nolan 3,*, Abdel-Mouttalib Ouagazzal 2,*, Emma L. Coghill 3, Karin Gale 5, Elisabetta Golini 4, Sylvie Jacquot 2, Wojtek Krezel 2, Andy Parker 3, Fabrice Riet 2, Ilka Schneider 1, Daniela Marazziti 4, Johan Auwerx 2, Steve D. M. Brown 3, Pierre Chambon 2, Nadia Rosenthal 5, Glauco Tocchini-Valentini 4 and Wolfgang Wurst 1

1 Gesellschaft für Strahlenforschung,{dagger}-National Research Center for Environment and Health, Institute of Developmental Genetics, Neuherberg, Germany
2 Institut Charles Sadron, Strasbourg, France
3 Medical Research Council, Harwell, United Kingdom
4 Consiglio Nazionale delle Ricerche-Institute of Cell Biology, Monterotondo, Italy
5 European Molecular Biology Laboratory, Monterotondo, Italy

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.

inbred mouse strains; test battery; open field; acoustic startle response; prepulse inhibition; rotarod; tail flick; SHIRPA; Y-maze; grip strength






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