RAI1 Mutant Mice Exhibit Smith-Magenis Syndrome Phenotypes

Smith-Magenis Syndrome (SMS) is a neurodevelopmental disorder that results from mutations in a specific region on chromosomes 17. Mutation within 17p11.2 cause SMS in about 1 in 25,000 people worldwide, however because of phenotypic similarity to autism the true prevalence may be close to 1 in 15,000. SMS is characterized by intellectual disability, delayed motor and speech functions, craniofacial abnormalities, sleep disturbances, and communication and social behavior abnormalities. One of the genes related to the presentation of SMS is the Retinoic Acid Induced 1 (RAI1) gene. Mutations within this gene are seen in about 30% of SMS patients. Our hypothesis was that a single gene mutation of only RAI1 would be sufficient for behavioral characteristics of SMS to manifest in mice. Five behavioral tests were performed to assess social behavior of the two groups of mice. The behavior and performance observed in the group of mice with a RAI1 mutation (RAI1) was compared to a group of mice with no mutation (WT) in that gene. The five tests targeted behavioral characteristics such as: sociability, levels of interest, compulsivity, and submissive tendencies. Our results indicated that the RAI1 mutant mice had significant differences from the WT mice, showing abnormal social behavioral and presenting with SMS phenotypes. All of these differences between the social tendencies and behaviors of the RAI1 mice are important as they parallel phenotypes seen in SMS patients.