Duplication of GTF2I results in separation anxiety in mice and humans

Am J Hum Genet. 2012 Jun 8;90(6):1064-70. doi: 10.1016/j.ajhg.2012.04.012. Epub 2012 May 10.


Duplication (dup7q11.23) and deletion (Williams syndrome) of chromosomal region 7q11.23 cause neurodevelopmental disorders with contrasting anxiety phenotypes. We found that 30% of 4- to 12-year-olds with dup7q11.23 but fewer than 5% of children with WS or in the general population met diagnostic criteria for a separation-anxiety disorder. To address the role of one commonly duplicated or deleted gene in separation anxiety, we compared mice that had varying numbers of Gtf2i copies. Relative to mouse pups with one or two Gtf2i copies, pups with additional Gtf2i copies showed significantly increased maternal separation-induced anxiety as measured by ultrasonic vocalizations. This study links the copy number of a single gene from 7q11.23 to separation anxiety in both mice and humans, highlighting the utility of mouse models in dissecting specific gene functions for genomic disorders that span many genes. This study also offers insight into molecular separation-anxiety pathways that might enable the development of targeted therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety, Separation / genetics*
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 7
  • Female
  • Gene Deletion
  • Gene Duplication*
  • Humans
  • Male
  • Mice
  • Models, Genetic
  • Phenotype
  • Time Factors
  • Transcription Factors, TFII / genetics*
  • Williams Syndrome / genetics


  • GTF2I protein, human
  • Gtf2i protein, mouse
  • Transcription Factors, TFII