ENU mutagenesis reveals a highly mutable locus on mouse Chromosome 4 that affects ear morphogenesis

Mammalian Genome : Official Journal of the International Mammalian Genome Society
A E KiernanJean-Louis Guénet

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 ...Continue Reading

Citations

May 22, 2007·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Peter L OliverKay E Davies
Mar 1, 2005·Journal of the Association for Research in Otolaryngology : JARO·Ken A MorrisKirk W Beisel
May 24, 2006·Journal of the Association for Research in Otolaryngology : JARO·Daniel R Calabrese, Timothy E Hullar
Sep 9, 2005·Microbiology and Molecular Biology Reviews : MMBR·Sabine P Cordes
Oct 27, 2009·The Journal of Clinical Investigation·Victoria RandallPeter J Scambler
Oct 13, 2011·BMC Neuroscience·Tomoko MakishimaScott Wood
Jan 1, 2014·Frontiers in Cellular Neuroscience·Wanda S Layman, Jian Zuo

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