title: Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media.
abstract: 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.
authors.affiliation: Mammalian Gentics Unit, Medical Research Council, Harwell, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Parkinson
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Hardisty-Hughes
authors.forename: Hilda
authors.initials: H
authors.lastname: Tateossian
authors.forename: Hsun-Tien
authors.initials: HT
authors.lastname: Tsai
authors.forename: Debra
authors.initials: D
authors.lastname: Brooker
authors.forename: Sue
authors.initials: S
authors.lastname: Morse
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Lalane
authors.forename: Francesca
authors.initials: F
authors.lastname: MacKenzie
authors.forename: Martin
authors.initials: M
authors.lastname: Fray
authors.forename: Pete
authors.initials: P
authors.lastname: Glenister
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Woodward
authors.forename: Sian
authors.initials: S
authors.lastname: Polley
authors.forename: Ivana
authors.initials: I
authors.lastname: Barbaric
authors.forename: Neil
authors.initials: N
authors.lastname: Dear
authors.forename: Tertius A
authors.initials: TA
authors.lastname: Hough
authors.forename: A Jackie
authors.initials: AJ
authors.lastname: Hunter
authors.forename: Michael T
authors.initials: MT
authors.lastname: Cheeseman
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D004432:Ear, Middle / Q000166:cytology / Q000473:pathology; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006098:Granulocytes / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000473:pathology; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009666:Nose / Q000166:cytology / Q000473:pathology; D010033:Otitis Media / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D011519:Proto-Oncogenes / Q000235:genetics*; D013047:Specific Pathogen-Free Organisms; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C499305:Mecom protein, mouse; D014157:Transcription Factors