TFII-I, a candidate gene for Williams syndrome cognitive profile: parallels between regional expression in mouse brain and human phenotype

Neuroscience. 2004;123(4):931-8. doi: 10.1016/j.neuroscience.2003.08.038.


The gene for TFII-I, a widely expressed transcription factor, has been localized to an interval of human chromosome 7q11.23 that is commonly deleted in Williams syndrome (WS). The clinical phenotype of WS includes elfin facies, infantile hypercalcemia, supravalvular aortic stenosis, hyperacusis and mental retardation. The WS cognitive profile (WSCP) is notable for the differential impairment of visual-spatial abilities with relative sparing of verbal-linguistic function. Fine mapping of individuals with WS has revealed a close association between deletion of TFII-I and the WSCP. To determine the plausibility of the hypothesis that hemizygous deletion of TFII-I contributes to the WSCP, we have examined the anatomic distribution of TFII-I RNA and protein isoforms in brains from adult and embryonic mice. Our studies show that early in development, TFII-I expression is widespread and nearly uniform throughout the brain. In adult brain, TFII-I protein is present exclusively in neurons. Highest levels of expression are observed in cerebellar Purkinje cells and in hippocampal interneurons. TFII-I immunoreactivity is distinct from that of the related protein, TFII-IRD1, which is also localized to the region of human chromosome 7 deleted in WS. The expression pattern of TFII-I in mouse brain parallels regions in human brain which have been shown to be anatomically and functionally altered in humans with WS. These observations are consistent with the hypothesis that deletion of the gene for TFII-I contributes to the cognitive impairments observed in WS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / growth & development
  • Brain / metabolism*
  • Cell Line
  • Embryo, Mammalian
  • Exons / physiology
  • Gene Expression*
  • Humans
  • Immunoblotting / methods
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Kidney
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism
  • Peptides / immunology
  • Phenotype*
  • Protein Isoforms / immunology
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Transcription Factors, TFII / genetics*
  • Transcription Factors, TFII / metabolism
  • Williams Syndrome / genetics*
  • Williams Syndrome / metabolism


  • Peptides
  • Protein Isoforms
  • RNA, Messenger
  • Transcription Factors, TFII