Characterization of a Novel Mouse Model of Restricted Repetitive Behaviors

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DESCRIPTION (provided by applicant): We have recently identified repetitive motor behaviors in the inbred C58/J mouse strain. This strain robustly displays repetitive behaviors such as jumping, flipping and weaving. The C58/J mouse strain is unique among currently used animal models for restrictive, repetitive behaviors (RRB) because these aberrant behaviors emerge spontaneously during the pre-weaning period and do not require pharmacological insult or environmental restriction, such as isolate-housing, as a trigger. In addition, C58/J is genotypically and phenotypically very similar to C57BL/6J, allowing this commonly used inbred strain to serve as an appropriate control. These characteristics make the C58/J mouse strain a potentially powerful animal model in the study of RRB. In order to further characterize the C58/J mouse strain as a model for RRB in humans, we will use a cross-fostering procedure to establish whether maternal behavior contributes to the emergence of RRB. Additionally, we will determine the efficacy of chronic pharmacological intervention on stereotyped responses in adult C58/J mice. Lastly, we will determine whether aberrant RRB is associated with structural changes in brain, using magnetic resonance imaging. At the present time, there are no well- validated animal models of RBB, a core feature of autism. This project will positively impact the field of autism spectrum disorder research by providing information on the neurobiology of aberrant behaviors in mice and by identifying whether the C58/J inbred strain is indeed an appropriate pre-clinical screen for human RRB, as well as strengthening the emerging field of brain structural imaging in rodents. PUBLIC HEALTH RELEVANCE: The proposed studies will evaluate the C58/J inbred mouse strain as a novel animal model for the study of restricted, repetitive behaviors relevant to autism. The aims will determine whether maternal behavior contributes to the emergence of repetitive behaviors during the neonatal or post-weaning period, and evaluate the efficacy of pharmacological agents against repetitive behaviors in adult C58/J mice. The final goal is to identify structural differences in the brains of C58/J mice using MRI technology.