title: ENU mutagenesis reveals a highly mutable locus on mouse Chromosome 4 that affects ear morphogenesis.
abstract: Chemical mutagenesis followed by screening for abnormal phenotypes in the mouse holds much promise as a method for revealing gene function. This method is particularly well-suited for discovering genes involved in hearing or balance function, as these defects are relatively easy to screen for in the mouse. We report here the inner ear abnormalities and genetic localization of seven new dominant mutations created by ENU mutagenesis. All seven mutant stocks were identified because of circling and/or head-weaving behavior, which is an indication of balance dysfunction. Investigation of the inner ears of the seven mutant stocks revealed very similar lateral and posterior semicircular canal defects. Studies of the development of the canals in one mutant stock revealed that the affected canals showed reduced outgrowth and delayed canal fusion. Physiological studies performed in one mutant stock showed raised average compound-action-potential thresholds of approximately 10-20 dB sound pressure level (SPL) (depending on frequency), indicating a mild hearing impairment, although scanning electron microscopy performed in several of the mutant stocks revealed no obvious structural defects in the organ of Corti. All seven mutations mapped to the proximal portion of Chromosome (Chr) 4, near the centromere. On the basis of their similar phenotype and map location, we suggest that the seven mutant genes may be allelic and represent a highly mutable locus on Chr 4 that may be particularly susceptible to ENU-induced mutation on the BALB/c genetic background.
authors.affiliation: MRC Institute of Hearing Research, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Kiernan
authors.forename: Alexandra
authors.initials: A
authors.lastname: Erven
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Voegeling
authors.forename: Jo
authors.initials: J
authors.lastname: Peters
authors.forename: Pat
authors.initials: P
authors.lastname: Nolan
authors.forename: Jackie
authors.initials: J
authors.lastname: Hunter
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Bacon
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guénet
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D002874:Chromosome Mapping; D003051:Cochlea / Q000002:abnormalities / Q000196:embryology*; D004432:Ear, Middle / Q000002:abnormalities / Q000196:embryology*; D005038:Ethylnitrosourea / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009024:Morphogenesis / Q000235:genetics; D009153:Mutagens / Q000494:pharmacology*; D012665:Semicircular Canals / Q000002:abnormalities / Q000196:embryology*
chemical_list: D000477:Alkylating Agents; D009153:Mutagens; D005038:Ethylnitrosourea