Abstract
Autism spectrum disorder (ASD) is characterized by deficits in social interaction, delays and impairments in communication, and restricted interests and repetitive behaviors. ASD is highly heritable, indicating genetic causal factors, but its rising prevalence also suggests environmental changes, such as expanding numbers of chemical pollutants. Putative risk factors for ASD include various environmental factors and mutations in any one of over 19,000 human genes.
To identify risk factors, scientists apply statistical approaches to identify factors associated with ASD, then employ laboratory animals, commonly rodents, to ascertain whether the association indicates a causal relationship. If a mouse strain with a targeted mutation or chemical exposure expresses autistic-like phenotypes, it can be used as a “mouse model of autism” to elucidate causal mechanisms and develop drug treatments. Such approaches were successfully employed to understand Retts and Fragile-X syndromes, disabilities sharing features with autism. This review describes the social features of ASD and their behavioral analogues in laboratory rodents. It also describes the genetic and chemical risk factors associated with ASD and the underlying epigenetic processes mediating their influence on brain development and social behavior.
Epigenetic processes are powerfully affected by life experience. Natural environments offer rodents a complex array of choices, contingencies, rewards, and punishments. By contrast, standard laboratory cages and so-called “enriched” cages offer rodents sparse spatial and temporal variation, precluding variety of affective experience or opportunity to exercise their naturally evolved capacities for decision-making. Paucity of life experience can irreversibly obstruct development and run at cross-purposes with efforts to identify risk factors and treatments for ASD. Alternatives to standard laboratory animal caging will be explored.
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Lahvis, G.P. (2016). Rodent Models of Autism, Epigenetics, and the Inescapable Problem of Animal Constraint. In: Gewirtz, J., Kim, YK. (eds) Animal Models of Behavior Genetics. Advances in Behavior Genetics. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3777-6_9
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