Autism: Animal Models

Abstract

Autism is a neurodevelopmental disorder characterised by deficits in social interaction, social communication, sensory abnormalities, stereotyped and repetitive behaviours, and restricted interests. Autism spectrum disorder (ASD) has proven difficult to study because of the diversity of its behavioural symptoms, complex genetics and lack of ubiquitous biomarkers. Progress in the development of heuristic animal models has allowed investigators to model some of the core symptoms of autism, including deficits in social interactions, aspects of social communication and stereotyped, repetitive behaviours. Specific hypotheses can now be formulated and tested in mouse, rat and non‐human primate models. Translational applications of animal models have advanced the discovery of therapeutic interventions for treating the core features of ASD. This article describes some of the major behavioural approaches and animal models designed to study neurodevelopmental disorders, with a focus on ASDs. Key Concepts Autism is a complex disorder whose underlying biology is being studied using rodent and non‐human primate animal models. Rodents and non‐human primates are social animals with rich and complex behavioural repertories that make them useful for modelling neurodevelopmental disorders. Many of the behaviours that reflect core deficits in autism, including social communication, social interaction, motor stereotypies and repetitive behaviours, can be modelled in rodents and non‐human primates. Inbred strains of mice can be used to discover genes important for the expression of complex behaviours and can provide insights into the neurobiology of social interactions and social communication. Mice and rats with targeted mutations in risk genes and deletions identified in people with autism provide research tools for investigating mechanistic substrates of the disorder and for discovering therapeutic interventions. Animal models of neurodevelopmental disorders, while important and useful, typically only model specific aspects of a disorder rather that recapitulating its full symptomatology.

New approaches to quantify social development in rhesus macaques (Macaca mulatta): Integrating eye tracking with traditional assessments of social behavior

“…The integration of eye tracking with traditional behavioral observations provides new insight into the development of social behavior and opens new translational research opportunities. Although reciprocal social interactions remain the gold standard for evaluating species‐typical social interactions (Bauman, Crawley, & Berman, 2019; Silverman, Yang, Lord, & Crawley, 2010), there are challenges in quantifying social interactions. First of all, it is difficult to accurately quantify social behavior, especially for primates, where social interactions entail subtle social cues that may be missed by observers.…”

The development of animal models for autism: A gene-environment approach

“…The apparent increase in prevalence over the past 20 years, the enormous burden to the patient and society, and the lack of effective pharmacological treatments have made ASD an increasing focus of research. Animal models play a major role in this research process, as they allow for the testing of specific hypotheses and the identification of novel therapies (Bauman et al, 2010). However, the recent rate of animal research translating into novel pharmacological therapies has been poor, particularly in the field of neuroscience (Kola & Landis, 2004).…”

“…Prenatal exposure to VPA has been thoroughly assessed as an animal model for ASD. In fact, prenatal exposure to VPA is now a well-established model for ASD and has been used in cell-cultures, tadpoles, zebrafish, and rodents (Bauman, Crawley, & Berman, 2010;Jacob et al, 2014;James et al, 2015;Kim et al, 2011;Miyazaki, Narita, & Narita, 2005;Patterson, 2011;Rodier, Ingram, Tisdale, & Croog, 1997;Schneider & Przewlocki, 2005). The typical method of creating this model is to inject pregnant rats with a single dose of VPA around the time of the foetal neural tube closure, approximately GD 12 (Kim et al, 2011).…”

“…Animal models play a major role in the research process of any disorder/disease, as they allow for the testing of specific hypotheses and the identification of novel therapies (Bauman et al, 2010). Although there is some disagreement on what constitutes a good animal model for a given disorder, a model's suitability is most often evaluated for three kinds of validity: construct, face, and predictive validity (Nestler & Hyman, 2010;Willner, 1984).…”

The development of animal models for autism: A gene-environment approach

“…Prenatal exposure to VPA has been thoroughly assessed as an animal model for ASD. In fact, prenatal exposure to VPA is now a well-established model for ASD and has been used in cell-cultures, tadpoles, zebrafish, and rodents (Bauman, Crawley, & Berman, 2010;Jacob et al, 2014;James et al, 2015;Kim et al, 2011;Miyazaki, Narita, & Narita, 2005;Patterson, 2011;Rodier, Ingram, Tisdale, & Croog, 1997;Schneider & Przewlocki, 2005). The typical method of creating this model is to inject pregnant rats with a single dose of VPA around the time of the foetal neural tube closure, approximately GD 12 (Kim et al, 2011).…”