title: Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study.
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.
authors.affiliation: Gesellschaft für Strahlenforschungdagger-National Research Center for Environment and Health, Institute of Developmental Genetics, Neuherberg, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mandillo
authors.forename: Valter
authors.initials: V
authors.lastname: Tucci
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
authors.forename: Hamid
authors.initials: H
authors.lastname: Meziane
authors.forename: Mumna Al
authors.initials: MA
authors.lastname: Banchaabouchi
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kallnik
authors.forename: Heena V
authors.initials: HV
authors.lastname: Lad
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Nolan
authors.forename: Abdel-Mouttalib
authors.initials: AM
authors.lastname: Ouagazzal
authors.forename: Emma L
authors.initials: EL
authors.lastname: Coghill
authors.forename: Karin
authors.initials: K
authors.lastname: Gale
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Golini
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jacquot
authors.forename: Wojtek
authors.initials: W
authors.lastname: Krezel
authors.forename: Andy
authors.initials: A
authors.lastname: Parker
authors.forename: Fabrice
authors.initials: F
authors.lastname: Riet
authors.forename: Ilka
authors.initials: I
authors.lastname: Schneider
authors.forename: Daniela
authors.initials: D
authors.lastname: Marazziti
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosenthal
authors.forename: Glauco
authors.initials: G
authors.lastname: Tocchini-Valentini
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D019411:Clinical Laboratory Techniques; D007391:International Cooperation; D007753:Laboratories; D008297:Male; D018782:Maze Learning; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013216:Reflex, Startle; D015203:Reproducibility of Results; D045442:Rotarod Performance Test