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

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

Research output: Contribution to journalArticlepeer-review

196 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)243-255
Number of pages13
JournalPhysiological Genomics
Volume34
Issue number3
DOIs
StatePublished - Aug 2008
Externally publishedYes

Keywords

  • Acoustic startle response
  • Grip strength
  • Inbred mouse strains
  • Open field
  • Prepulse inhibition
  • Rotarod
  • SHIRPA
  • Tail flick
  • Test battery
  • Y-maze

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