Duplication and deletion of a common interval spanning 26 genes on chromosome 7q11.23 cause Dup7q11.23 Syndrome and Williams-Beuren Syndrome, neurodevelopmental disorders with contrasting anxiety phenotypes. The General Transcription Factor 2 I (GTF2I) gene has been implicated in separation anxiety, common in people with Dup7q11.23, and we studied the effects of commonly used anxiolytics on maternal separation-induced USV in mouse models with copy number changes in Gtf2i. Subcutaneous injection of saline affected both USV production and plasma corticosterone levels in a Gtf2i gene-dosage dependent manner. Drugs acting on the glutamate receptors were most effective at attenuating USVs in all genotypes, compared to GABAergic and serotonergic modulators. Brain c-fos expression after separation was reduced by a GABAA agonist, but not a glutamate antagonist. Collectively, these results suggest a potential difference in pain sensitivity based on Gtf2i copy number and implicate the glutamatergic and GABAergic systems in anxiety phenotypes in these two disorders.

Duplication and deletion of a common interval spanning 26 genes on chromosome 7q11.23 cause Dup7q11.23 Syndrome and Williams-Beuren Syndrome, neurodevelopmental disorders with contrasting anxiety phenotypes. The General Transcription Factor 2 I (GTF2I) gene has been implicated in separation anxiety, common in people with Dup7q11.23, and we studied the effects of commonly used anxiolytics on maternal separation-induced USV in mouse models with copy number changes in Gtf2i. Subcutaneous injection of saline affected both USV production and plasma corticosterone levels in a Gtf2i gene-dosage dependent manner. Drugs acting on the glutamate receptors were most effective at attenuating USVs in all genotypes, compared to GABAergic and serotonergic modulators. Brain c-fos expression after separation was reduced by a GABAA agonist, but not a glutamate antagonist. Collectively, these results suggest a potential difference in pain sensitivity based on Gtf2i copy number and implicate the glutamatergic and GABAergic systems in anxiety phenotypes in these two disorders.