A null mutation of mouse Kcna10 causes significant vestibular and mild hearing dysfunction

Sue I. Lee, Travis Conrad, Sherri M Jones, Ayala Lagziel, Matthew F. Starost, Inna A. Belyantseva, Thomas B. Friedman, Robert J. Morell

Research output: Contribution to journalArticle

13 Citations (Scopus)

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-Kcna10TM45, 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. Kcna10TM45 homozygotes display only a mild elevation in pure tone hearing thresholds as measured by auditory brainstem response (ABR), while heterozygotes are normal. However, Kcna10TM45 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 Kcna10TM45 targeted allele may be a model of human nonsyndromic vestibulopathy.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalHearing Research
Volume300
DOIs
StatePublished - Jun 1 2013

Fingerprint

Homozygote
Inner Ear
beta-Galactosidase
Outer Auditory Hair Cells
Evoked Potentials
Inner Auditory Hair Cells
Hearing
Vestibular Hair Cells
Voltage-Gated Potassium Channels
Organ of Corti
Mutation
Brain Stem Auditory Evoked Potentials
Heterozygote
Exons
Alleles
Proteins

ASJC Scopus subject areas

  • Sensory Systems
  • Medicine(all)

Cite this

Lee, S. I., Conrad, T., Jones, S. M., Lagziel, A., Starost, M. F., Belyantseva, I. A., ... Morell, R. J. (2013). A null mutation of mouse Kcna10 causes significant vestibular and mild hearing dysfunction. Hearing Research, 300, 1-9. https://doi.org/10.1016/j.heares.2013.02.009

A null mutation of mouse Kcna10 causes significant vestibular and mild hearing dysfunction. / Lee, Sue I.; Conrad, Travis; Jones, Sherri M; Lagziel, Ayala; Starost, Matthew F.; Belyantseva, Inna A.; Friedman, Thomas B.; Morell, Robert J.

In: Hearing Research, Vol. 300, 01.06.2013, p. 1-9.

Research output: Contribution to journalArticle

Lee, SI, Conrad, T, Jones, SM, Lagziel, A, Starost, MF, Belyantseva, IA, Friedman, TB & Morell, RJ 2013, 'A null mutation of mouse Kcna10 causes significant vestibular and mild hearing dysfunction', Hearing Research, vol. 300, pp. 1-9. https://doi.org/10.1016/j.heares.2013.02.009
Lee, Sue I. ; Conrad, Travis ; Jones, Sherri M ; Lagziel, Ayala ; Starost, Matthew F. ; Belyantseva, Inna A. ; Friedman, Thomas B. ; Morell, Robert J. / A null mutation of mouse Kcna10 causes significant vestibular and mild hearing dysfunction. In: Hearing Research. 2013 ; Vol. 300. pp. 1-9.
@article{41f0b902633b47919f8c6aefd8d92c87,
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-Kcna10TM45, 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. Kcna10TM45 homozygotes display only a mild elevation in pure tone hearing thresholds as measured by auditory brainstem response (ABR), while heterozygotes are normal. However, Kcna10TM45 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 Kcna10TM45 targeted allele may be a model of human nonsyndromic vestibulopathy.",
author = "Lee, {Sue I.} and Travis Conrad and Jones, {Sherri M} and Ayala Lagziel and Starost, {Matthew F.} and Belyantseva, {Inna A.} and Friedman, {Thomas B.} and Morell, {Robert J.}",
year = "2013",
month = "6",
day = "1",
doi = "10.1016/j.heares.2013.02.009",
language = "English (US)",
volume = "300",
pages = "1--9",
journal = "Hearing Research",
issn = "0378-5955",
publisher = "Elsevier",

}

TY - JOUR

T1 - A null mutation of mouse Kcna10 causes significant vestibular and mild hearing dysfunction

AU - Lee, Sue I.

AU - Conrad, Travis

AU - Jones, Sherri M

AU - Lagziel, Ayala

AU - Starost, Matthew F.

AU - Belyantseva, Inna A.

AU - Friedman, Thomas B.

AU - Morell, Robert J.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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-Kcna10TM45, 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. Kcna10TM45 homozygotes display only a mild elevation in pure tone hearing thresholds as measured by auditory brainstem response (ABR), while heterozygotes are normal. However, Kcna10TM45 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 Kcna10TM45 targeted allele may be a model of human nonsyndromic vestibulopathy.

AB - 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-Kcna10TM45, 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. Kcna10TM45 homozygotes display only a mild elevation in pure tone hearing thresholds as measured by auditory brainstem response (ABR), while heterozygotes are normal. However, Kcna10TM45 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 Kcna10TM45 targeted allele may be a model of human nonsyndromic vestibulopathy.

UR - http://www.scopus.com/inward/record.url?scp=84876476477&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876476477&partnerID=8YFLogxK

U2 - 10.1016/j.heares.2013.02.009

DO - 10.1016/j.heares.2013.02.009

M3 - Article

VL - 300

SP - 1

EP - 9

JO - Hearing Research

JF - Hearing Research

SN - 0378-5955

ER -