Consistent hypersocial behavior in mice carrying a deletion of Gtf2i but no evidence of hyposocial behavior with Gtf2i duplication: Implications for Williams-Beuren syndrome and autism spectrum disorder.

Introduction:Williams-Beuren syndrome (WBS) is a developmental disorder caused by hemizygous deletion of human chromosome 7q11.23. Hypersocial behavior is one symptom of WBS and contrasts with hyposociality observed in autism spectrum disorder (ASD). Interestingly, duplications of 7q11.23 have been associated with ASD. The social phenotype of WBS has been linked to GTF2I or general transcription factor IIi (TFII-I). Duplication of GTF2I has also been associated with ASD. Methods:We compared mice having either a deletion (Gtf2i ) or duplication (Gtf2i ) of Gtf2i to wild-type (Gtf2i ) littermate controls in a series of behavioral tasks including open-field activity monitoring, olfactory probes, a social choice task, social transmission of food preference, habituation-dishabituation, and operant social motivation paradigms. Results:In open-field observations, Gtf2i and Gtf2i mice demonstrated normal activity and thigmotaxis, and surprisingly, each strain showed a significant preference for a stimulus mouse that was not observed in Gtf2i siblings. Both Gtf2i and Gtf2i mice demonstrated normal olfaction in buried food probes, but the Gtf2i mice spent significantly more time investigating urine scent versus water, which was not observed in the other strains. Gtf2i mice also spent significantly more time in nose-to-nose contact compared to Gtf2i siblings during the open-field encounter of the social transmission of food preference task. In operant tasks of social motivation, Gtf2i mice made significantly more presses for social rewards than Gtf2i siblings, while there was no difference in presses for the Gtf2i mice. Discussion:Results were remarkably consistent across testing paradigms supporting a role for GTF2i in the hypersocial phenotype of WBS and more broadly in the regulation of social behavior. Support was not observed for the role of GTF2i in ASD.

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