Behavioural phenotyping assays for mouse models of autism

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Abstract
Autism is a neurodevelopmental disorder that is diagnosed by the presence of three categories of behavioural criteria: first, unusual reciprocal social interactions; second, deficits in communication; and third, stereotyped, repetitive behaviours with restricted interests. Behavioural phenotyping of mouse models of autism requires assays that are relevant to each of the three categories of the core symptoms. Optimal animal models incorporate phenotypes that are analogous to the human disease (face validity). They should also incorporate the same cause as the human disease (construct validity), and ameliorative responses that are specific to treatments that are efficacious in the human disease (predictive validity). Robust phenotypes in mouse models of autism that have face validity and construct validity hold great promise as translational tools for discovering effective therapeutics for components of autism spectrum disorders. Mus musculus is a social species that engages in high levels of reciprocal social interactions. Assays for deficits in sociability include the three-chambered social approach test, the partition test, observer-scored parameters of reciprocal social interactions and tests of social transmission of food preference. Communication in mice is not well understood, but assays to investigate this include olfactory discrimination, urinary scent marking and countermarking, and assays of ultrasonic vocalizations in social settings. Assays for repetitive behaviours and restricted interests in mice include measures of motor stereotypies, repetitive self-grooming and perseverative spatial habits in learning tasks that include the T-maze and Morris water maze. Control parameters that assess general health, motor functions and sensory abilities (for example, olfactory detection of pheromones) are essential for ruling out artefacts that could confound the interpretation of social, communication or repetitive phenotypes.