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. 2017 Dec 19;8(1):e00895.
doi: 10.1002/brb3.895. eCollection 2018 Jan.

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

Loren A Martin  1 , Erica Iceberg  1 , Gabriel Allaf  2
Affiliations

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

Loren A Martin et al. Brain Behav. .

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 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+/dup ) 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+/dup 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+/dup 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+/dup 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.

Keywords: 7q11.23; TFII‐I; Williams syndrome; autism; social motivation.

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Figures

Figure 1
Figure 1
(a) Mean distance traveled and time spent in perimeter versus center of a novel open‐field environment. All four genotypes traveled similar distances and demonstrated a preference for the perimeter versus the center zones. (b) Mean time spent in stimulus mouse corner versus empty cup corner. The Gtf2i +/+ mice did not show a corner preference, but the Gtf2i +/− mice and the Gtf2i +/dup mice spent significantly more time in the stimulus mouse corner than the empty cup corner. Asterisks indicate significance where p < .05
Figure 2
Figure 2
Mean time spent in each trial investigating a social stimulus partner. While the pattern was similar between mouse strains, the Gtf2i +/− mice demonstrated increased time spent in exploration of the social partner during trial 2 compared to Gtf2i +/+ siblings. There was no significant difference in time spent with a social partner between the Gtf2i +/dup mice and their Gtf2i +/+ siblings. For the dishabituation trial, all four mouse strains demonstrated the predicted rebound in social exploration time from the previous trial
Figure 3
Figure 3
Mean time spent in nose‐to‐nose contact with demonstrator mouse during the STFP paradigm. Gtf2i +/− mice spent significantly more time in nose‐to‐nose contact than Gtf2i +/+ siblings. There was no significant difference in nose‐to‐nose contact between the Gtf2i +/dup mice and their Gtf2i +/+ siblings. Asterisks indicate significance where p < .05
Figure 4
Figure 4
(a) Mean latency to find buried food. There were no significant differences between genotypes in the latency to find the buried Cocoa Puff. (b) Mean time spent in urine and water zones. Gtf2i +/− mice spent significantly more time in the urine zone versus the water zone, but there were no significant differences for the Gtf2i +/+ mice. There was no significant difference in time spent in the urine zone versus the water zone between the Gtf2i +/dup mice and their Gtf2i +/+ siblings. Asterisks indicate significance where p < .05
Figure 5
Figure 5
(a) Mean breakpoint (last reinforced ratio) achieved before the mice stopped lever pressing for 5 min. Gtf2i +/− mice demonstrated a significantly higher breakpoint than Gtf2i +/+ siblings. There was no significant difference in breakpoint between the Gtf2i +/dup mice and their Gtf2i +/+ siblings. (b) Mean number of presses for each type of reward. There was a significant preference for food over social rewards for both genotypes. However, Gtf2i +/− mice demonstrated significantly fewer food presses and made a significantly higher percentage of presses for social rewards than Gtf2i +/+ siblings. There was no significant difference in percentage of presses for food and social rewards between the Gtf2i +/dup mice and their Gtf2i +/+ siblings. Asterisks indicate significance where p < .05
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References

    1. Association , A. P. (2013). Diagnostic and statistical manual of mental disorders. Arlington, VA: American Psychiatric Publishing.
    1. Bariselli, S. , Tzanoulinou, S. , Glangetas, C. , Prevost‐Solie, C. , Pucci, L. , Viguie, J. , … Bellone, C. (2016). SHANK3 controls maturation of social reward circuits in the VTA. Nature Neuroscience, 19, 926–934. https://doi.org/10.1038/nn.4319 - DOI - PMC - PubMed
    1. Bayes, M. , Magano, L. F. , Rivera, N. , Flores, R. , & Perez Jurado, L. A. (2003). Mutational mechanisms of Williams‐Beuren syndrome deletions. American Journal of Human Genetics, 73, 131–151. https://doi.org/10.1086/376565 - DOI - PMC - PubMed
    1. Bellugi, U. , Adolphs, R. , Cassady, C. , & Chiles, M. (1999). Towards the neural basis for hypersociability in a genetic syndrome. NeuroReport, 10, 1653–1657. https://doi.org/10.1097/00001756-199906030-00006 - DOI - PubMed
    1. Bellugi, U. , Korenberg, J. R. , & Klima, E. (2001). Williams Syndrome: An exploration of neurocognitive and genetic features. Clinical Neuroscience Research, 1, 217–229. https://doi.org/10.1016/S1566-2772(01)00008-1 - DOI

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