Animal models of restricted repetitive behavior in autism

Abstract

Restricted, repetitive behavior, along with deficits in social reciprocity and communication, is diagnostic of autism. Animal models relevant to this domain generally fall into three classes: repetitive behavior associated with targeted insults to the CNS; repetitive behavior induced by pharmacological agents; and repetitive behavior associated with restricted environments and experience. The extant literature provides potential models of the repetitive behavioral phenotype in autism rather than attempts to model the etiology or pathophysiology of restricted, repetitive behavior, as these are poorly understood. This review focuses on our work with deer mice which exhibit repetitive behaviors associated with environmental restriction. Repetitive behaviors are the most common category of abnormal behavior observed in confined animals and larger, more complex environments substantially reduce the development and expression of such behavior. Studies with this model, including environmental enrichment effects, suggest alterations in cortical-basal ganglia circuitry in the development and expression of repetitive behavior. Considerably more work needs to be done in this area, particularly in modeling the development of aberrant repetitive behavior. As mutant mouse models continue to proliferate, there should be a number of promising genetic models to pursue.

Social approach and repetitive behavior in eleven inbred mouse strains

“…The responses were remarkably similar in form to stereotypy reported for deer mice housed in standard cages [39,40]. Enriched housing can reduce the levels of stereotypy and delay the emergence of aberrant motor responses in the deer mice, as well as in other animal models of repetitive behavior [23]. It is possible that the standard, ventilated caging system used to house mice in the present study might have contributed to the high levels of spontaneous stereotypy in the C58/J strain.…”

The Prevalence and Phenomenology of Repetitive Behavior in Genetic Syndromes

“…Mutations in this specific region are associated with Prader-Willi and Angelman syndromes both of which are reported to show increased levels of repetitive behaviour. Other mutant mouse models with links to Down Syndrome and obsessive compulsive disorder have also been reported to show increased rates of repetitive and stereotyped behaviour (Lewis, Tanimura & Bodfish., 2007). To date, these associations between aetiology and behavior are largely speculative.…”

Advances in behavioral genetics: mouse models of autism

“…3 Determining whether a proposed mouse model for autism recapitulates one or more of the core clinical symptoms can provide valuable insight as to the functional impact of altered genes or environment. [12][13][14][15][16] However, the development of mouse behavioral assays for detecting aberrant social responses, restricted interests, or repetitive behavior reflective of autism has proved challenging. Our research group has proposed a set of behavioral tests that can be used to assess social deficits and repetitive behavior in mice.…”

“…17,[20][21][22] The symptom of repetitive behavior encompasses both 'lower-order' motoric stereotypy and self-injury, and 'higher-order' responses reflecting general cognitive rigidity, such as restricted, obsessive interests and strong resistance to environmental change. 13,23,24 Both components of the repetitive behavior domain tend to co-occur in children with autism or related disorders. 23,[25][26][27] A recent study examining the relationship between core symptoms of autism in twins provided evidence that, while highly heritable, the domains of social impairment and repetitive behavior were genetically heterogeneous.…”

“…28,29 These findings raise the intriguing possibility that mouse models reflecting different components of the autism behavioral phenotype might be used to distinguish the specific genetic pathways that mediate stereotypy and cognitive inflexibility from those underlying deficiencies in social interaction or communication. Lewis et al 13 provide a comprehensive overview of animal models for repetitive behavior, including both the lower-order and higher-order response clusters. In our characterization of inbred mouse strains, we have used home cage observations to detect persistent, stereotyped motoric behavior.…”