The Shank3-InsG3680(+/+) mouse model of autism spectrum disorder displays auditory avoidance in a novel behavioral test

Ana Margarida Gonçalves; Nuno Sousa; Luis Jacinto; Patricia Monteiro

doi:10.3389/fnbeh.2023.1205507

The Shank3-InsG3680(+/+) mouse model of autism spectrum disorder displays auditory avoidance in a novel behavioral test

Front Behav Neurosci. 2023 Aug 24:17:1205507. doi: 10.3389/fnbeh.2023.1205507. eCollection 2023.

Authors

Ana Margarida Gonçalves^{1

2}, Nuno Sousa^{1

2}, Luis Jacinto³, Patricia Monteiro^{1

2

3}

Affiliations

¹ Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal.
² ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
³ Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal.

Abstract

Introduction: Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, repetitive behaviors, and sensory alterations, with auditory hypersensitivity being one of the most commonly reported sensory-perceptual abnormalities. Several candidate genes for involvement in this disorder have emerged from patient studies, including SHANK3, a gene that encodes a protein (SHANK3) in the postsynaptic density of excitatory synapses. Previous work has shown that mutant mice carrying a human ASD mutation in the Shank3 gene (InsG3680) exhibit repetitive behaviors and social interaction deficits, indicating important construct and face validity for this genotype as an animal model of ASD.

Methods: To further address whether these mice also present auditory sensory-perceptual alterations, we developed a novel behavioral test in which mice can choose between different soundscapes.

Results: Our results reveal that, in comparison to wild-type mice, Shank3 mutants display a strong behavioral preference toward silent regions of the arena.

Discussion: These data suggest that Shank3- mutant mice might express an auditory hypersensitivity phenotype, further adding to the face validity of this genotype as an animal model of ASD.

Keywords: Shank3; animal model; auditory hypersensitivity; autism spectrum disorder (ASD); behavior; sensory alterations.

Grants and funding

This work was funded by the FEBS (Federation of European Biochemical Societies) Excellence Awards 2021 and by Fundação para a Ciência e a Tecnologia (FCT, Portugal) projects 2022.05228.PTDC, PTDC/MED-NEU/28073/2017 (POCI-01-0145-FEDER-028073), 2021.01032.CEECIND, UIDB/50026/2020, and UIDP/50026/2020. LJ was supported by “la Caixa” Banking Foundation under the grant agreement LCF/PR/HR21-00410. AG was supported by a doctoral fellowship (PD/BD/137759/2018) from FCT as part of the Inter-University Doctoral Program in Ageing and Chronic Disease (PhDOC).