Rai1 Haploinsufficiency Is Associated with Social Abnormalities in Mice

Abstract

<i>Background:</i> Autism is characterized by difficulties in social interaction, communication, and repetitive behaviors; with different degrees of severity in each of the core areas. Haploinsufficiency and point mutations of <i>RAI1</i> are associated with Smith-Magenis syndrome (SMS), a genetic condition that scores within the autism spectrum range for social responsiveness and communication, and is characterized by neurobehavioral abnormalities, intellectual disability, developmental delay, sleep disturbance, and self-injurious behaviors. <i>Methods:</i> To investigate the relationship between <i>Rai1</i> and social impairment, we evaluated the <i>Rai1^+/-</i> mice with a battery of tests to address social behavior in mice. <i>Results:</i> We found that the mutant mice showed diminished interest in social odors, abnormal submissive tendencies, and increased repetitive behaviors when compared to wild type littermates. <i>Conclusions:</i> These findings suggest that <i>Rai1</i> contributes to social behavior in mice, and prompt it as a candidate gene for the social behaviors observed in Smith-Magenis Syndrome patients.