Repetitive behaviors in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context

Background: Autism spectrum disorder (ASD) is characterized by persistent deficits in social behavior and communication, together with restricted and repetitive patterns of behavior. Several ASD candidate genes have been identified, including the SHANK gene family with its three family members SHANK1, SHANK2, and SHANK3. Methods: Typically, repetitive behavior in mouse models for ASD is assessed by measuring self-grooming behavior. The first aim of the current study was to assess repetitive behaviors in Shank1(-/-) null mutant, Shank1(+/-) heterozygous, and Shank1(+/+) wildtype littermate control mice by means of a comprehensive approach, including the assessment of self-grooming, digging behavior, and marble burying. The second aim was to establish a test paradigm that allows for assessing the effects of social context on the occurrence of repetitive behaviors in a genotype-dependent manner. To this aim, repetitive behaviors were repeatedly tested on three consecutive days in distinct social contexts, namely in presence or absence of social odors. Results: Shank1(+/-) heterozygous and to a lesser extent Shank1(-/-) null mutant mice displayed slightly elevated levels of self-grooming behavior as adults, but not as juveniles, with genotype differences being most prominent in the social context. In contrast to elevated self-grooming behavior, marble burying was strongly reduced in adult Shank1(+/-) heterozygous and Shank1(-/-) null mutant mice across social contexts, as compared to adult Shank1(+/+) wildtype littermate controls. Conclusion: The opposite effects of the Shank1 deletion on the two types of repetitive behaviors are in line with a number of studies on repetitive behaviors in other genetic Shank models. (C) 2014 Elsevier B.V. All rights reserved.