Skip to main content
JARO: Journal of the Association for Research in Otolaryngology logoLink to JARO: Journal of the Association for Research in Otolaryngology
. 2002 Oct 31;4(2):130–138. doi: 10.1007/s10162-002-3015-9

The Deaf Mouse Mutant Jeff (Jf) is a Single Gene Model of Otitis Media

Rachel E Hardisty 1, Alexandra Erven 2, Karen Logan 1, Susan Morse 1, Sylvia Guionaud 3, Sara Sancho–Oliver 3, A Jackie Hunter 4, Steve D M Brown 1,, Karen P Steel 2
PMCID: PMC3202714  PMID: 12943368

Abstract

Otitis media is the most common cause of hearing impairment in children and is primarily characterized by inflammation of the middle ear mucosa. Yet nothing is known of the underlying genetic pathways predisposing to otitis media in the human population. Increasingly, large-scale mouse mutagenesis programs have undertaken systematic and genome-wide efforts to recover large numbers of novel mutations affecting a diverse array of phenotypic areas involved with genetic disease including deafness. As part of the UK mutagenesis program, we have identified a novel deaf mouse mutant, Jeff (Jf). Jeff maps to the distal region of mouse chromosome 17 and presents with fluid and pus in the middle ear cavity. Jeff mutants are 21% smaller than wild-type littermates, have a mild craniofacial abnormality, and have elevated hearing thresholds. Middle ear epithelia of Jeff mice show evidence of a chronic proliferative otitis media. The Jeff mutant should prove valuable in elucidating the underlying genetic pathways predisposing to otitis media.

Keywords: otitis media, deafness, ENU mutagenesis, mouse genetics

Full Text

The Full Text of this article is available as a PDF (561.6 KB).

Acknowledgements

This work was funded by the Medical Research Council, GlaxoSmithKline, and the European Community (contract BMH4-CT97-2715). Thanks to Terry Hacker, Caroline Barker, and Adele Seymour for histology services; Peter Glenister, Claire Shearer, and Sian Clements for IVF; and Professor Mark Haggard and Mary Gannon for advice on human OME.

References

  • 1.Ball SS, Prazma J, Dais CG, Triana RJ, Pillsbury HC. Role of tumor necrosis factor and interleukin-1 in endotoxin-induced middle ear effusions. Ann. Otol. Rhinol. Laryngol. 1997;106:633–639. doi: 10.1177/000348949710600803. [DOI] [PubMed] [Google Scholar]
  • 2.Berry CL, Vogler C, Galvin NJ, Birkenmeier EH, Sly WS. Pathology of the ear in murine mucopolysaccharidosis type VII. Morphological correlates of hearing loss. Lab. Invest. 1994;71:438–445. [PubMed] [Google Scholar]
  • 3.Brown SDM, Balling R. Systematic approaches to mouse mutagenesis. Curr. Opin. Genet. Dev. 2001;11:268–273. doi: 10.1016/S0959-437X(00)00189-1. [DOI] [PubMed] [Google Scholar]
  • 4.Brown SDM, Steel KP (2002) DFN genes. In: Creighton TE (ed) Encyclopedia of Molecular Medicine. John Wiley & Sons, New York, pp 1035–1038
  • 5.Casselbrant ML, Mandel EM, Fall PA, Rockette HE, Kurs–Lasky M, Bluestone CD, Ferrell RE. The heritability of otitis media. A twin and triplet study. JAMA. 1999;282:2125–2130. doi: 10.1001/jama.282.22.2125. [DOI] [PubMed] [Google Scholar]
  • 6.Davidson J, Hyde ML, Alberti PW. Epidemiologic parameters in childhood hearing loss: a review. Int. J. Pediatr. Otorhinolaryngol. 1989;17:239–266. doi: 10.1016/0165-5876(89)90051-7. [DOI] [PubMed] [Google Scholar]
  • 7.DeMaria TF, Murwin DM. Tumor necrosis factor during experimental lipopolysaccharide-induced otitis media. Laryngoscope. 1997;107:369–372. doi: 10.1097/00005537-199703000-00017. [DOI] [PubMed] [Google Scholar]
  • 8.Goodman MG, Weigle WO. T cell regulation of polyclonal B cell responsiveness II. Evidence for a deficit in T cell function in mice with an X-linked B lymphocyte defect. J. Immunol. 1979;123:2482–2487. [PubMed] [Google Scholar]
  • 9.Hardisty RE, Mburu P, Brown SDM. mutagenesis and the search for deafness genes. Br. J. Audiol. 1999;33:279–283. doi: 10.3109/03005369909090110. [DOI] [PubMed] [Google Scholar]
  • 10.Hrabe de Angelis M, Faswinkel H, Fuchs H, Rathkolb B, Soearto D, Marschall S, Heffner S, Pargent W, Wuensch K, Jung M, Reis A, Richter T, Alessandrini F, Jakob T, Fuchs E, Kolb H, Kremmer E, Schaeble K, Rollinski B, Roscher A, Peters C, Meitinger T, Astrom T, Steckler T, Holsboer F, Klopstock T, Gekeler F, Schindewolf C, Jung T, Avraham K, Behrendt H, Ring J, Zimmer A, Schughart K, Pfeffer K, Wolf E, Balling R. Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat. Genet. 2000;25:444–447. doi: 10.1038/78146. [DOI] [PubMed] [Google Scholar]
  • 11.Hunter SE, Singla AK, Prazma J, Jewett BS, Randell SH, Pillsbury HC. Mucin production in the middle ear in response to lipopolysaccharides. Otolaryngol. Head Neck Surg. 1999;120:884–888. doi: 10.1016/S0194-5998(99)70331-1. [DOI] [PubMed] [Google Scholar]
  • 12.Ichimiya I, Yoshida K, Hirano T, Suzuki M, Mogi G. Significance of spiral ligament fibrocytes with cochlear inflammation. Int. J. Pediatr. Otorhinolaryngol. 2000;56:45–51. doi: 10.1016/S0165-5876(00)00408-0. [DOI] [PubMed] [Google Scholar]
  • 13.Isaacs AM, Davies KE, Hunter AJ, Nolan PM, Vizor L, Peters J, Gale DG, Kelsell DP, Latham ID, Chase JM, Fisher EMC, Bouzyk M, Potter A, Masih M, Walsh FS, Sims MA, Doncaster KE, Parsons CA, Martin J, Brown SDM, Rastan S, Spurr N, Gray IC. Identification of two new Pmp22 mouse mutants using large-scale mutagenesis and a novel rapid mapping strategy. Hum. Mol. Genet. 2000;9:1865–1871. doi: 10.1093/hmg/9.12.1865. [DOI] [PubMed] [Google Scholar]
  • 14.Johnson IJ, Brooks T, Hutton DA, Birchall JP, Pearson JP. Compositional differences between bilateral middle ear effusions in OME: Evidence for a different aetiology. Laryngoscope. 1997;107:684–689. doi: 10.1097/00005537-199705000-00024. [DOI] [PubMed] [Google Scholar]
  • 15.Kubba H, Pearson JP, Birchall JP. The aetiology of otitis media with effusion: a review. Clin. Otolaryngol. 2000;25:181–194. doi: 10.1046/j.1365-2273.2000.00350.x. [DOI] [PubMed] [Google Scholar]
  • 16.Kuijpers W, Van der Beek JMH, Jap PHK, Tonnaer ELG. The structure of the middle ear epithelium of the rat and the effect of eustachian tube obstruction. Histochem. J. 1984;16:807–818. doi: 10.1007/BF01002787. [DOI] [PubMed] [Google Scholar]
  • 17.Mawson SR. Diseases of the ear, 3rd ed. London: Edward Arnold Publishers Ltd.; 1974. pp. 284–285. [Google Scholar]
  • 18.Maxwell KS, Fitzgerald JE, Burleson JA, Leonard G, Carpenter R, Kreutzer DL. Interleukin 8 expression in Otitis Media. Laryngoscope. 1994;104:989–995. doi: 10.1288/00005537-199408000-00013. [DOI] [PubMed] [Google Scholar]
  • 19.McGinn MD, Bean–Knudsen D, Ermel R. Incidence of otitis media in CBA/J and CBA/CaJ mice. Hear. Res. 1992;59:1–6. doi: 10.1016/0378-5955(92)90094-4. [DOI] [PubMed] [Google Scholar]
  • 20.Mitchell CR, Kempton JB, Scott–Tyler B, Trune DR. Otitis media incidence and impact on the auditory brain stem response in lipopolysaccharide-nonresponsive C3H/HeJ mice. Otolaryngol. Head Neck Surg. 1997;117:459–464. doi: 10.1016/S0194-59989770014-7. [DOI] [PubMed] [Google Scholar]
  • 21.Nadeau J, Balling R, Barsh G, Beier D, Brown SDM, Bucan M, Camper S, Carlson G, Copeland N, Epping J, Fletcher C, Frankel WN, Ganten D, Goldowitz D, Goodnow C, Guenet JL, Hicks G, Hrabe de Angelis M, Jackson I, Jacon HJ, Jenkins N, Johnson D, Justice M, Kay S, Kingsley D, Lehrah H, Magnuson T, Meisler M, Poustka A, Rinchik E, Rossant J, Russell LB, Schimenti J, Shiroishi T, Skarnes WC, Soriano P, Stanford W, Takahashi JS, Wurst W. Functional annotation of mouse genome sequences. Science. 2001;291:1251–1255. doi: 10.1126/science.1058244. [DOI] [PubMed] [Google Scholar]
  • 22.Nolan PM, Peters J, Strivens M, Rogers D, Hagan J, Spurr N, Gray IC, Vizor L, Brooker D, Whitehill E, Washbourne R, Hough T, Greenaway S, Hewitt M, Liu X, McCormack S, Pickford K, Selley R, Wells S, Tymowska–Lalane Z, Roby P, Glenister P, Thornton C, Thaung C, Stevenson J-A, Arkell R, Mburu P, Hardisty R, Kiernan A, Erven A, Steel KP, Vogeling S, Guenet J, Nickols C, Sadri R, Naase M, Isaacs AM, Davies K, Browne M, Fisher EMC, Martin J, Rastan S, Brown SDM, Hunter AJ. A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse. Nat. Genet. 2000;25:440–443. doi: 10.1038/78140. [DOI] [PubMed] [Google Scholar]
  • 23.Paparella MM. Interactive inner ear/middle ear disease, including perilymphatic fistula. Acta Otolaryngol. Suppl. 1991;485:36–45. doi: 10.3109/00016489109128042. [DOI] [PubMed] [Google Scholar]
  • 24.Rose AS, Prazma J, Randell SH, Baggett HC, Lane AP, Pillsbury HC. Nitric oxide mediates mucin secretion in endotoxin-induced otitis media with effusion. Otolaryngol. Head Neck Surg. 1997;116:308–316. doi: 10.1016/S0194-59989770265-1. [DOI] [PubMed] [Google Scholar]
  • 25.Schmidt–Ullrich R, Aebischer T, Hulsken J, Birchmeier W, Klemm U, Scheidereit C. Requirement of NF-kB/Rel for the development of hair follicles and other epidermal appendices. Development. 2001;128:3843–3853. doi: 10.1242/dev.128.19.3843. [DOI] [PubMed] [Google Scholar]
  • 26.Self T, Mahony M, Fleming J, Walsh J, Brown SDM, Steel KP. Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells. Development. 1998;125:557–566. doi: 10.1242/dev.125.4.557. [DOI] [PubMed] [Google Scholar]
  • 27.Steel KP, Moorjani P, Bock GR. Mixed conductive and sensorineural hearing loss in LP/J mice. Hear. Res. 1987;28:227–236. doi: 10.1016/0378-5955(87)90051-7. [DOI] [PubMed] [Google Scholar]
  • 28.Steel KP, Smith RJH. Normal hearing in splotch (Sp/+), the mouse homologue of Waardenburg syndrome type 1. Nat. Genet. 1992;2:75–79. doi: 10.1038/ng0992-75. [DOI] [PubMed] [Google Scholar]
  • 29.Steel KP, Cros K. A genetic approach to understanding auditory function. Nat. Genet. 2001;27:143–149. doi: 10.1038/84758. [DOI] [PubMed] [Google Scholar]
  • 30.Yang A, Walker N, Bronson R, Kaghad M, Oosterwegel M, Bonnin J, Vagner C, Bonnet H, Dikkes P, Sharpe A, McKeon F, Caput D. p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours. Nature. 2000;404:99–103. doi: 10.1038/35003607. [DOI] [PubMed] [Google Scholar]

Articles from JARO: Journal of the Association for Research in Otolaryngology are provided here courtesy of Association for Research in Otolaryngology

RESOURCES