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- Title
Consistent hypersocial behavior in mice carrying a deletion of <italic>Gtf2i</italic> but no evidence of hyposocial behavior with <italic>Gtf2i</italic> duplication: Implications for Williams–Beuren syndrome and autism spectrum disorder.
- Authors
Martin, Loren A.; Iceberg, Erica; Allaf, Gabriel
- Abstract
Abstract: 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 <italic>GTF2I</italic> or general transcription factor IIi (<italic>TFII‐I</italic>). Duplication of <italic>GTF2I</italic> has also been associated with ASD. Methods: We compared mice having either a deletion (<italic>Gtf2i</italic><italic>+/−</italic>) or duplication (<italic>Gtf2i</italic><italic>+/dup</italic>) of <italic>Gtf2i</italic> to wild‐type (<italic>Gtf2i</italic><italic>+/+</italic>) 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, <italic>Gtf2i</italic><italic>+/−</italic> and <italic>Gtf2i</italic><italic>+/dup</italic> mice demonstrated normal activity and thigmotaxis, and surprisingly, each strain showed a significant preference for a stimulus mouse that was not observed in <italic>Gtf2i</italic><italic>+/+</italic> siblings. Both <italic>Gtf2i</italic><italic>+/−</italic> and <italic>Gtf2i</italic><italic>+/dup</italic> mice demonstrated normal olfaction in buried food probes, but the <italic>Gtf2i</italic><italic>+/−</italic> mice spent significantly more time investigating urine scent versus water, which was not observed in the other strains. <italic>Gtf2i</italic><italic>+/−</italic> mice also spent significantly more time in nose‐to‐nose contact compared to <italic>Gtf2i</italic><italic>+/+</italic> siblings during the open‐field encounter of the social transmission of food preference task. In operant tasks of social motivation, <italic>Gtf2i</italic><italic>+/−</italic> mice made significantly more presses for social rewards than <italic>Gtf2i</italic><italic>+/+</italic> siblings, while there was no difference in presses for the <italic>Gtf2i</italic><italic>+/dup</italic> mice. Discussion: Results were remarkably consistent across testing paradigms supporting a role for <italic>GTF2i</italic> in the hypersocial phenotype of WBS and more broadly in the regulation of social behavior. Support was not observed for the role of <italic>GTF2i</italic> in ASD.
- Subjects
AUTISM spectrum disorders; WILLIAMS syndrome; HUMAN chromosome abnormalities; DELETION mutation; PHENOTYPES; GENETICS
- Publication
Brain & Behavior, 2018, Vol 8, Issue 1, p1
- ISSN
2162-3279
- Publication type
Article
- DOI
10.1002/brb3.895