Otitis media in a new mouse model for CHARGE syndrome with a deletion in the Chd7 gene

PLoS One. 2012;7(4):e34944. doi: 10.1371/journal.pone.0034944. Epub 2012 Apr 23.


Otitis media is a middle ear disease common in children under three years old. Otitis media can occur in normal individuals with no other symptoms or syndromes, but it is often seen in individuals clinically diagnosed with genetic diseases such as CHARGE syndrome, a complex genetic disease caused by mutation in the Chd7 gene and characterized by multiple birth defects. Although otitis media is common in human CHARGE syndrome patients, it has not been reported in mouse models of CHARGE syndrome. In this study, we report a mouse model with a spontaneous deletion mutation in the Chd7 gene and with chronic otitis media of early onset age accompanied by hearing loss. These mice also exhibit morphological alteration in the Eustachian tubes, dysregulation of epithelial proliferation, and decreased density of middle ear cilia. Gene expression profiling revealed up-regulation of Muc5ac, Muc5b and Tgf-β1 transcripts, the products of which are involved in mucin production and TGF pathway regulation. This is the first mouse model of CHARGE syndrome reported to show otitis media with effusion and it will be valuable for studying the etiology of otitis media and other symptoms in CHARGE syndrome.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • CHARGE Syndrome / genetics*
  • CHARGE Syndrome / metabolism
  • CHARGE Syndrome / pathology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Ear, Middle / pathology
  • Eustachian Tube / metabolism
  • Eustachian Tube / pathology
  • Exons
  • Gene Expression Profiling
  • Genotype
  • Hearing Loss / etiology
  • Heterozygote
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mucins / genetics
  • Mucins / metabolism
  • Otitis Media / genetics*
  • Otitis Media / metabolism
  • Otitis Media / pathology
  • Phenotype
  • Sequence Deletion
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation


  • Chd7 protein, mouse
  • DNA-Binding Proteins
  • Mucins
  • Transforming Growth Factor beta1