Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss.

Age-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominant...

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Autores principales:	Neil J Ingham, Navid Banafshe, Clarisse Panganiban, Julia L Crunden, Jing Chen, Morag A Lewis, Karen P Steel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29fd16cc5705416aa5aa7a1a41a8a36e
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spelling	oai:doaj.org-article:29fd16cc5705416aa5aa7a1a41a8a36e2021-12-02T20:17:24ZInner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss.1932-620310.1371/journal.pone.0258158https://doaj.org/article/29fd16cc5705416aa5aa7a1a41a8a36e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258158https://doaj.org/toc/1932-6203Age-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominantly low-frequency recessive hearing impairment in two mutant mouse lines carrying different mutant alleles of the Klhl18 gene: a spontaneous missense mutation (Klhl18lowf) and a targeted mutation (Klhl18tm1a(KOMP)Wtsi). Both males and females were studied, and the two mutant lines showed similar phenotypes. Threshold for auditory brainstem responses (ABR; a measure of auditory nerve and brainstem neural activity) were normal at 3 weeks old but showed progressive increases from 4 weeks onwards. In contrast, distortion product otoacoustic emission (DPOAE) sensitivity and amplitudes (a reflection of cochlear outer hair cell function) remained normal in mutants. Electrophysiological recordings from the round window of Klhl18lowf mutants at 6 weeks old revealed 1) raised compound action potential thresholds that were similar to ABR thresholds, 2) cochlear microphonic potentials that were normal compared with wildtype and heterozygous control mice and 3) summating potentials that were reduced in amplitude compared to control mice. Scanning electron microscopy showed that Klhl18lowf mutant mice had abnormally tapering of the tips of inner hair cell stereocilia in the apical half of the cochlea while their synapses appeared normal. These results suggest that Klhl18 is necessary to maintain inner hair cell stereocilia and normal inner hair cell function at low frequencies.Neil J InghamNavid BanafsheClarisse PanganibanJulia L CrundenJing ChenMorag A LewisKaren P SteelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258158 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Neil J Ingham Navid Banafshe Clarisse Panganiban Julia L Crunden Jing Chen Morag A Lewis Karen P Steel Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss.
description	Age-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominantly low-frequency recessive hearing impairment in two mutant mouse lines carrying different mutant alleles of the Klhl18 gene: a spontaneous missense mutation (Klhl18lowf) and a targeted mutation (Klhl18tm1a(KOMP)Wtsi). Both males and females were studied, and the two mutant lines showed similar phenotypes. Threshold for auditory brainstem responses (ABR; a measure of auditory nerve and brainstem neural activity) were normal at 3 weeks old but showed progressive increases from 4 weeks onwards. In contrast, distortion product otoacoustic emission (DPOAE) sensitivity and amplitudes (a reflection of cochlear outer hair cell function) remained normal in mutants. Electrophysiological recordings from the round window of Klhl18lowf mutants at 6 weeks old revealed 1) raised compound action potential thresholds that were similar to ABR thresholds, 2) cochlear microphonic potentials that were normal compared with wildtype and heterozygous control mice and 3) summating potentials that were reduced in amplitude compared to control mice. Scanning electron microscopy showed that Klhl18lowf mutant mice had abnormally tapering of the tips of inner hair cell stereocilia in the apical half of the cochlea while their synapses appeared normal. These results suggest that Klhl18 is necessary to maintain inner hair cell stereocilia and normal inner hair cell function at low frequencies.
format	article
author	Neil J Ingham Navid Banafshe Clarisse Panganiban Julia L Crunden Jing Chen Morag A Lewis Karen P Steel
author_facet	Neil J Ingham Navid Banafshe Clarisse Panganiban Julia L Crunden Jing Chen Morag A Lewis Karen P Steel
author_sort	Neil J Ingham
title	Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss.
title_short	Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss.
title_full	Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss.
title_fullStr	Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss.
title_full_unstemmed	Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss.
title_sort	inner hair cell dysfunction in klhl18 mutant mice leads to low frequency progressive hearing loss.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/29fd16cc5705416aa5aa7a1a41a8a36e
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Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss.

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