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

TreatmentAmountAdministration routeAdministration time

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

Published in Biological Psychiatry 2015:

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.

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.

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.

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.

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