Strategies for Assessing Autistic-Like Behaviors in Mice

Summary

Rodent models are valuable tools for studying core behaviors related to autism spectrum disorder (ASD). In this article, we expound on two behavioral tests for modeling the core features of ASD in mice: self-grooming, which assesses repetitive behavior, and the three-chamber social interaction test, which documents social impairments.

Abstract

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social communication impairments and restrictive or repetitive behaviors, such as hand flapping or lining up objects. These behavioral patterns can be reliably observed in mouse models with ASD-linked genetic mutations, making them highly useful tools for studying the underlying cellular and molecular mechanisms in ASD. Understanding how genetic changes affect the neurobiology and behaviors observed in ASD will facilitate the development of novel targeted therapeutic compounds to ameliorate core behavioral impairments. Our lab has employed several protocols encompassing well-described training and testing procedures that reflect a wide range of behavioral deficits related to ASD. Here, we detail two assays to study the core features of ASD in mouse models: self-grooming (a measure of repetitive behavior) and the three-chamber social interaction test (a measure of social interaction approach and preference for social novelty).

Introduction

Autism spectrum disorder (ASD) is a developmental brain disorder that manifests social communication or interaction impairments and restricted, repetitive patterns of behaviors or interests^1,2. In 2022, approximately 1 in 100 children were diagnosed with ASD globally³. According to the Centers for Disease Control and Prevention (CDC, USA), the prevalence of ASD has increased by 30% since 2008 and is up more than 2-fold since 2000^4,5. Individuals with ASD may also exhibit co-morbidities, such as intellectual disability (ID) (35.2....

Protocol

All procedures and experiments involving animal subjects were approved by the Facility Animal Care Committee (FACC) regulations, which follow the guidelines established by the Canadian Council on Animal Care, the McGill University Animal Care Committee, and the NIH Office of Laboratory Animal Welfare (OLAW). The Public Health Service (PHS) Assurance number for McGill University is F-16-00005(A5006-01).

1. Animal preparation

1. Test mice: Select 2-3 month (8 to 13 week.......

Discussion

Most etiological causes, pathological changes, and biological markers of ASD are not known or available. ASD diagnosis is primarily based on two established sets of clinical symptoms: persistent deficits in social communication and excessive repetitive behaviors^18,19,55. Given that ASD is a spectrum disorder encompassing a wide range of symptoms, it is challenging to fully reproduce ASD symptoms in experimental animals. Neverthe.......

Materials

Name	Company	Catalog Number	Comments
1/4'' Teklad Corncob Bedding	Harlan, TEKLAD	7092-7097	The raw stock for corncob bedding products  is 100% corncob. No other components or additives are used.
HD Video Recording Cameratraditional Video Camera	Sony	HDRCX405	50 Mbps XAVC S1 1920 x 1080 at 60P, AVCHD and MP4 codecs. 30x Optical / 60x Clear Image Zoom to get closer to the action. 26.8 mm wide angle ZEISS Lens.
Nitrile Powder Free Examination Gloves	Aurelia, Transform	ASTM D6319-00	Tested for use with Chemotherapy drugs per ASTM D6978
Rodent Plastic Cage Bottoms	Ancare	AN75PLF	AN75 Mouse 7½” W x 11½” L x 5” H
TÅGARP floor lamp and bulbs	IEKA	604.640.49	Bulbs are 23 W 120 V.
Ugo Basile Sociability Apparatus	Stoelting	60450	The Sociability Apparatus (3-chambered social test) is a valuable tool to study social behaviour in mice.
Versa-Clean	Fisherbrand	PVCLN04	Cleaning agent
Whiteboard and  Low Odor Dry Erase Marker	EXPO	NA	Dry erase markers in bold black