Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media

PLoS Genet. 2006 Oct 6;2(10):e149. doi: 10.1371/journal.pgen.0020149.


Otitis media (OM), inflammation of the middle ear, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population and mouse models that there is a significant genetic component predisposing to OM, yet nothing is known about the underlying genetic pathways involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This develops from acute OM that arises spontaneously in the postnatal period, with the age of onset and early severity dependent on the microbiological status of the mice and their air quality. We have identified the causal mutation, a missense change in the C-terminal zinc finger region of the transcription factor Evi1. This protein is expressed in middle ear basal epithelial cells, fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when inflammatory changes are underway. The identification and characterization of the Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates a new pathway in genetic predisposition to OM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA Mutational Analysis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Ear, Middle / cytology
  • Ear, Middle / pathology
  • Flow Cytometry
  • Genetic Predisposition to Disease / genetics*
  • Granulocytes / immunology
  • Lung / cytology
  • Lung / pathology
  • MDS1 and EVI1 Complex Locus Protein
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation / genetics*
  • Nose / cytology
  • Nose / pathology
  • Otitis Media / genetics*
  • Otitis Media / immunology
  • Phenotype
  • Proto-Oncogenes / genetics*
  • Specific Pathogen-Free Organisms
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • MDS1 and EVI1 Complex Locus Protein
  • Mecom protein, mouse
  • Transcription Factors