title: Sheltering behavior and locomotor activity in 11 genetically diverse common inbred mouse strains using home-cage monitoring.
abstract: Functional genetic analyses in mice rely on efficient and in-depth characterization of the behavioral spectrum. Automated home-cage observation can provide a systematic and efficient screening method to detect unexplored, novel behavioral phenotypes. Here, we analyzed high-throughput automated home-cage data using existing and novel concepts, to detect a plethora of genetic differences in spontaneous behavior in a panel of commonly used inbred strains (129S1/SvImJ, A/J, C3H/HeJ, C57BL/6J, BALB/cJ, DBA/2J, NOD/LtJ, FVB/NJ, WSB/EiJ, PWK/PhJ and CAST/EiJ). Continuous video-tracking observations of sheltering behavior and locomotor activity were segmented into distinguishable behavioral elements, and studied at different time scales, yielding a set of 115 behavioral parameters of which 105 showed highly significant strain differences. This set of 115 parameters was highly dimensional; principal component analysis identified 26 orthogonal components with eigenvalues above one. Especially novel parameters of sheltering behavior and parameters describing aspects of motion of the mouse in the home-cage showed high genetic effect sizes. Multi-day habituation curves and patterns of behavior surrounding dark/light phase transitions showed striking strain differences, albeit with lower genetic effect sizes. This spontaneous home-cage behavior study demonstrates high dimensionality, with a strong genetic contribution to specific sets of behavioral measures. Importantly, spontaneous home-cage behavior analysis detects genetic effects that cannot be studied in conventional behavioral tests, showing that the inclusion of a few days of undisturbed, labor extensive home-cage assessment may greatly aid gene function analyses and drug target discovery.
authors.affiliation: Sylics (Synaptologics BV), Amsterdam, The Netherlands; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Loos
authors.affiliation: Sylics (Synaptologics BV), Amsterdam, The Netherlands.
authors.forename: Bastijn
authors.initials: B
authors.lastname: Koopmans
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Emmeke
authors.initials: E
authors.lastname: Aarts
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gregoire
authors.initials: G
authors.lastname: Maroteaux
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands; Section Complex Trait Genetics, Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Sophie
authors.initials: S
authors.lastname: van der Sluis
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands; Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
mesh_terms: D000204:Activity Cycles / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D009043:Motor Activity / Q000235:genetics*; D013045:Species Specificity