Dlgap1 knockout mice exhibit alterations of the postsynaptic density and selective reductions in sociability

The scaffold protein DLGAP1 is localized at the post-synaptic density (PSD) of glutamatergic neurons and is a component of supramolecular protein complexes organized by PSD95. Gain-of-function variants of DLGAP1 have been associated with obsessive-compulsive disorder (OCD), while haploinsufficient v...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2018-02, Vol.8 (1), p.2281-12, Article 2281
Main Authors: Coba, M. P., Ramaker, M. J., Ho, E. V., Thompson, S. L., Komiyama, N. H., Grant, S. G. N., Knowles, J. A., Dulawa, S. C.
Format: Article
Language:English
Subjects:
631/378/2583
631/378/3919
82
82/1
82/58
82/80
Animals
Autism
Behavior, Animal
Female
Glutamatergic transmission
Humanities and Social Sciences
Male
Mental disorders
Mice, Knockout
multidisciplinary
Nest building
Neurons - pathology
Obsessive compulsive disorder
Post-Synaptic Density - pathology
Postsynaptic density
Postsynaptic density proteins
Protein Binding
Protein interaction
Proteins
Rodents
SAP90-PSD95 Associated Proteins - deficiency
Schizophrenia
Science
Science (multidisciplinary)
Social Behavior
Sucrose
Synaptic density
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The scaffold protein DLGAP1 is localized at the post-synaptic density (PSD) of glutamatergic neurons and is a component of supramolecular protein complexes organized by PSD95. Gain-of-function variants of DLGAP1 have been associated with obsessive-compulsive disorder (OCD), while haploinsufficient variants have been linked to autism spectrum disorder (ASD) and schizophrenia in human genetic studies. We tested male and female Dlgap1 wild type (WT), heterozygous (HT), and knockout (KO) mice in a battery of behavioral tests: open field, dig, splash, prepulse inhibition, forced swim, nest building, social approach, and sucrose preference. We also used biochemical approaches to examine the role of DLGAP1 in the organization of PSD protein complexes. Dlgap1 KO mice were most notable for disruption of protein interactions in the PSD, and deficits in sociability. Other behavioral measures were largely unaffected. Our data suggest that Dlgap1 knockout leads to PSD disruption and reduced sociability, consistent with reports of DLGAP1 haploinsufficient variants in schizophrenia and ASD.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-20610-y