title: A mutation in the F-box gene, Fbxo11, causes otitis media in the Jeff mouse.
abstract: Otitis media (OM), inflammation of the middle ear, is the most common cause of hearing impairment and surgery in children. Recurrent and chronic forms of OM are known to have a strong genetic component, but nothing is known of the underlying genes involved in the human population. We have previously identified a novel semi-dominant mouse mutant, Jeff, in which the heterozygotes develop chronic suppurative OM (Hardisty, R.E., Erven, A., Logan, K., Morse, S., Guionaud, S., Sancho-Oliver, S., Hunter, A.J., Brown, S.D. and Steel, K.P. (2003) The deaf mouse mutant Jeff (Jf) is a single gene model of otitis media. J. Assoc. Res. Otolaryngol., 4, 130-138.) and represent a model for chronic forms of OM in humans. We demonstrate here that Jeff carries a mutation in an F-box gene, Fbxo11. Fbxo11 is expressed in epithelial cells of the middle ears from late embryonic stages through to day 13 of postnatal life. In contrast to Jeff heterozygotes, Jeff homozygotes show cleft palate, facial clefting and perinatal lethality. We have also isolated and characterized an additional hypomorphic mutant allele, Mutt. Mutt heterozygotes do not develop OM but Mutt homozygotes also show facial clefting and cleft palate abnormalities. FBXO11 is one of the first molecules to be identified, contributing to the genetic aetiology of OM. In addition, the recessive effects of mutant alleles of Fbxo11 identify the gene as an important candidate for cleft palate studies in the human population.
authors.affiliation: MRC Mammalian Genetics Unit, Harwell, UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Hardisty-Hughes
authors.forename: Hilda
authors.initials: H
authors.lastname: Tateossian
authors.forename: Susan A
authors.initials: SA
authors.lastname: Morse
authors.forename: M Rosario
authors.initials: MR
authors.lastname: Romero
authors.forename: Alice
authors.initials: A
authors.lastname: Middleton
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Tymowska-Lalanne
authors.forename: A Jackie
authors.initials: AJ
authors.lastname: Hunter
authors.forename: Michael
authors.initials: M
authors.lastname: Cheeseman
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D044783:F-Box Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006720:Homozygote; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010033:Otitis Media / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D044783:F-Box Proteins; C515669:Fbxo11 protein, mouse; C481381:JF protein, mouse; D011506:Proteins