Mice overexpressing genes from the 22q11 region deleted in velo-cardio-facial syndrome/DiGeorge syndrome have middle and inner ear defects

Birgit Funke, Jonathan A. Epstein, Lazaros K. Kochilas, Min Min Lu, Raj K. Pandita, Jun Liao, Ralf Bauerndistel, Tanja Schüler, Hubert Schorle, M. Christian Brown, Joe Adams, Bernice E. Morrow

Research output: Contribution to journalArticle

71 Scopus citations


Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS) is a congenital anomaly disorder associated with hemizygous 22q11 deletions. We previously showed that bacterial artificial chromosome (BAC) transgenic mice overexpressing four transgenes, PNUTL1, (CDCrel-1), GP1Bβ, TBX1 and WDR14, had reduced viability, cardiovascular malformations and thymus gland hypoplasia. Since these are hallmark features of VCFS/DGS, we analyzed the mice for additional anomalies. We found that the mice have important defects in the middle and inner ear that are directly relevant to the disorder. The most striking defect was the presence of chronic otitis media, a common finding in VCFS/DGS patients. In addition, the mice had a hyperactive circling behavior and sensorineural hearing loss. This was associated with middle and inner ear malformations, analogous to Mondini dysplasia in humans reported to occur in VCFS/DGS patients. We propose that overexpression of one or more of the transgenes is responsible for the etiology of the ear defects in the mice. Based upon its pattern of expression in the ear and functional studies of the gene, TbX1 likely plays a central role. Haploinsufficiency of TBX1 may be responsible for ear disorders in VCFS/DGS patients.

Original languageEnglish (US)
Pages (from-to)2549-2556
Number of pages8
JournalHuman molecular genetics
Issue number22
Publication statusPublished - Oct 15 2001


ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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