Genetic mapping in mice reveals the involvement of Pcdh9 in long-term social and object recognition and sensorimotor development

Hilgo Bruining, Asuka Matsui, Asami Oguro-Ando, René S. Kahn, Heleen M. Van'T Spijker, Guus Akkermans, Oliver Stiedl, Herman Van Engeland, Bastijn Koopmans, Hein A. Van Lith, Hugo Oppelaar, Liselotte Tieland, Lourens J. Nonkes, Takeshi Yagi, Ryosuke Kaneko, J. Peter H. Burbach, Nobuhiko Yamamoto, Martien J. Kas, LJ Nonkes

    Research output: Contribution to journalArticleAcademicpeer-review

    29 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)485-495
    Number of pages11
    JournalBiological Psychiatry
    Volume78
    Issue number7
    DOIs
    Publication statusPublished - 1 Oct 2015

    Keywords

    • Associative learning
    • Autism spectrum disorder
    • Genetic mapping
    • Information processing
    • Pcdh9
    • QTL
    • Quantitative trait locus
    • Recognition
    • Sensory cortex
    • Social cognition

    Cite this