Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study.
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.
Mandillo
Silvia
S
Gesellschaft für Strahlenforschungdagger-National Research Center for Environment and Health, Institute of Developmental Genetics, Neuherberg, Germany.
Tucci
Valter
V
Hölter
Sabine M
SM
Meziane
Hamid
H
Banchaabouchi
Mumna Al
MA
Kallnik
Magdalena
M
Lad
Heena V
HV
Nolan
Patrick M
PM
Ouagazzal
Abdel-Mouttalib
AM
Coghill
Emma L
EL
Gale
Karin
K
Golini
Elisabetta
E
Jacquot
Sylvie
S
Krezel
Wojtek
W
Parker
Andy
A
Riet
Fabrice
F
Schneider
Ilka
I
Marazziti
Daniela
D
Auwerx
Johan
J
Brown
Steve D M
SD
Chambon
Pierre
P
Rosenthal
Nadia
N
Tocchini-Valentini
Glauco
G
Wurst
Wolfgang
W
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