Experiment name: Genetic mapping in mice reveals the involvement of Pcdh9 in long-term social and object recognition, and sensorimotor development. (Bruining 2015)
LSID: http://syli.cz/urn:lsid:public.sylics.com:experiment:4D68-9568-G5A3

Treatment	Amount	Administration route	Administration time

Treatment info:
Order of behavioural testing
Acoustic Startle Response and Prepulse Inhibition

Published in Biological Psychiatry 2015:
http://linkinghub.elsevier.com/retrieve/pii/S0006322315000876

Genetic mapping in mice reveals the involvement of Pcdh9 in long-term social and object recognition, and sensorimotor development
Hilgo Bruining (a, b), Asuka Matsui (c), Asami Oguro-Ando (a), René S. Kahn (b), Heleen M. van t Spijker (a), Guus Akkermans (a), Oliver Stiedl (d), Herman van Engeland (b), Bastijn Koopmans (e), Hein A. van Lith (f), Hugo Oppelaar (a), Liselotte Tieland (a), Lourens J. Nonkes (a), Takeshi Yagi (g), Ryosuke Kaneko (g), J. Peter H. Burbach (a), Nobuhiko Yamamoto (c), Martien J. Kas (a)
a Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
b Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
c Neuroscience Laboratories, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
d Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam
e Sylics (Synaptologics BV), Amsterdam, The Netherlands
f Division of Animal Welfare & Laboratory Animal Science, Department of Animals in Science and Society, Program Emotion and Cognition, Faculty of Veterinary Medicine, Utrecht University, The Netherlands
g KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.

Abstract
Background
Quantitative genetic analysis of basic mouse behaviors is a powerful tool to identify novel genetic phenotypes contributing to neurobehavioral disorders. Here, we analyzed genetic contributions to single-trial, long-term social and nonsocial recognition and subsequently studied the functional impact of an identified candidate gene on behavioral development.

Methods
Genetic mapping of single-trial social recognition was performed in chromosome substitution strains, a sophisticated tool for detecting quantitative trait loci (QTL) of complex traits. Follow-up occurred by generating and testing knockout (KO) mice of a selected QTL candidate gene. Functional characterization of these mice was performed through behavioral and neurological assessments across developmental stages and analyses of gene expression and brain morphology.

Results
Chromosome substitution strain 14 mapping studies revealed an overlapping QTL related to long-term social and object recognition harboring Pcdh9, a cell-adhesion gene previously associated with autism spectrum disorder. Specific long-term social and object recognition deficits were confirmed in homozygous (KO) Pcdh9-deficient mice, while heterozygous mice only showed long-term social recognition impairment. The recognition deficits in KO mice were not associated with alterations in perception, multi-trial discrimination learning, sociability, behavioral flexibility, or fear memory. Rather, KO mice showed additional impairments in sensorimotor development reflected by early touch-evoked biting, rotarod performance, and sensory gating deficits. This profile emerged with structural changes in deep layers of sensory cortices, where Pcdh9 is selectively expressed.

Conclusions
This behavior-to-gene study implicates Pcdh9 in cognitive functions required for long-term social and nonsocial recognition. This role is supported by the involvement of Pcdh9 in sensory cortex development and sensorimotor phenotypes.


Mouse info:

Mouse ID	Strain	Coat color	Genotype	Ear tag	Internal ID	Sex	Date of Birth	Sub experiment 1	Sub experiment 2	Sub experiment 3
PH11755	Pcdh9	black	hom		1063	male	17-03-2014
PH11756	Pcdh9	black	hom		1061	male	17-03-2014
PH11757	Pcdh9	black	hom		1065	male	17-03-2014
PH11758	Pcdh9	black	hetro		1066	male	17-03-2014
PH11759	Pcdh9	black	hom		1071	male	31-03-2014
PH11760	Pcdh9	black	hom		1072	male	31-03-2014
PH11761	Pcdh9	black	hetro		1073	male	31-03-2014
PH11762	Pcdh9	black	hetro		1074	male	31-03-2014
PH11763	Pcdh9	black	WT		1080	male	15-04-2014
PH11764	Pcdh9	black	hom		1082	male	15-04-2014
PH11765	Pcdh9	black	hetro		1083	male	15-04-2014
PH11766	Pcdh9	black	hetro		1091	male	16-04-2014
PH11767	Pcdh9	black	hom		1092	male	16-04-2014
PH11768	Pcdh9	black	hetro		1095	male	26-04-2014
PH11769	Pcdh9	black	hom		1096	male	26-04-2014
PH11770	Pcdh9	black	hetro		1097	male	26-04-2014
PH11771	Pcdh9	black	WT		1098	male	26-04-2014
PH11772	Pcdh9	black	hetro		1103	male	28-04-2014
PH11773	Pcdh9	black	WT		1104	male	28-04-2014
PH11774	Pcdh9	black	WT		1116	male	28-05-2014
PH11775	Pcdh9	black	WT		1117	male	28-05-2014
PH11776	Pcdh9	black	hetro		1119	male	28-05-2014
PH11777	Pcdh9	black	WT		1120	male	28-05-2014
PH11778	Pcdh9	black	WT		1132	male	01-06-2014
PH11779	Pcdh9	black	hom		1133	male	17-06-2014
PH11780	Pcdh9	black	hetro		1134	male	17-06-2014
PH11781	Pcdh9	black	hom		1136	male	17-06-2014
PH11782	Pcdh9	black	hom		1140	male	18-06-2014
PH11783	Pcdh9	black	hetro		1141	male	18-06-2014
PH11784	Pcdh9	black	hom		1142	male	18-06-2014
PH11785	Pcdh9	black	hetro		1143	male	18-06-2014
PH11786	Pcdh9	black	WT		476	male	04-05-2014
PH11787	Pcdh9	black	WT		477	male	04-05-2014
PH11788	Pcdh9	black	WT		489	male	16-06-2014
PH11789	Pcdh9	black	WT		490	male	16-06-2014