title: A null mutation of mouse Kcna10 causes significant vestibular and mild hearing dysfunction.
abstract: KCNA10 is a voltage gated potassium channel that is expressed in the inner ear. The localization and function of KCNA10 was studied in a mutant mouse, B6-Kcna10(TM45), in which the single protein coding exon of Kcna10 was replaced with a beta-galactosidase reporter cassette. Under the regulatory control of the endogenous Kcna10 promoter and enhancers, beta-galactosidase was expressed in hair cells of the vestibular organs and the organ of Corti. KCNA10 expression develops in opposite tonotopic gradients in the inner and outer hair cells. Kcna10(TM45) homozygotes display only a mild elevation in pure tone hearing thresholds as measured by auditory brainstem response (ABR), while heterozygotes are normal. However, Kcna10(TM45) homozygotes have absent vestibular evoked potentials (VsEPs) or elevated VsEP thresholds with prolonged peak latencies, indicating significant vestibular dysfunction despite the lack of any overt imbalance behaviors. Our results suggest that Kcna10 is expressed primarily in hair cells of the inner ear, with little evidence of expression in other organs. The Kcna10(TM45) targeted allele may be a model of human nonsyndromic vestibulopathy.
authors.affiliation: Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Ct, 2A-19, Rockville, MD 20850, USA.
authors.forename: Sue I
authors.initials: SI
authors.lastname: Lee
authors.forename: Travis
authors.initials: T
authors.lastname: Conrad
authors.forename: Sherri M
authors.initials: SM
authors.lastname: Jones
authors.forename: Ayala
authors.initials: A
authors.lastname: Lagziel
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Starost
authors.forename: Inna A
authors.initials: IA
authors.lastname: Belyantseva
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Morell
mesh_terms: D000161:Acoustic Stimulation; D000595:Amino Acid Sequence; D000818:Animals; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold; D016057:Evoked Potentials, Auditory, Brain Stem; D020022:Genetic Predisposition to Disease; D006198:Hair Cells, Auditory / Q000378:metabolism*; D006311:Hearing Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006720:Homozygote; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time; D051637:Shaker Superfamily of Potassium Channels / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D015837:Vestibular Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D058585:Vestibular Evoked Myogenic Potentials; D014722:Vestibule, Labyrinth / Q000378:metabolism* / Q000503:physiopathology
chemical_list: C574338:KCNA10 protein, mouse; D012333:RNA, Messenger; D051637:Shaker Superfamily of Potassium Channels