Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1

Yukako Asai, Bifeng Pan, Carl Nist-Lund, Alice Galvin, Andrei N. Lukashkin, Victoria A. Lukashkina, Tianwen Chen, Wu Zhou, Hong Zhu, Ian J. Russell, Jeffrey R. Holt, Gwenaelle S.G. Géléoc

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Recent work has demonstrated that transmembrane channel-like 1 protein (TMC1) is an essential component of the sensory transduction complex in hair cells of the inner ear. A closely related homolog, TMC2, is expressed transiently in the neonatal mouse cochlea and can enable sensory transduction in Tmc1-null mice during the first postnatal week. Both TMC1 and TMC2 are expressed at adult stages in mouse vestibular hair cells. The extent to which TMC1 and TMC2 can substitute for each other is unknown. Several biophysical differences between TMC1 and TMC2 suggest these proteins perform similar but not identical functions. To investigate these differences, and whether TMC2 can substitute for TMC1 in mature hair cells, we generated a knock-in mouse model allowing Cre-inducible expression of Tmc2. We assayed for changes in hair cell sensory transduction and auditory and vestibular function in Tmc2 knockin mice (Tm[Tmc2]) in the presence or absence of endogenous Tmc1, Tmc2 or both. Our results show that expression of Tm[TMC2] restores sensory transduction in vestibular hair cells and transiently in cochlear hair cells in the absence of TMC1. The cellular rescue leads to recovery of balance but not auditory function. We conclude that TMC1 provides some additional necessary function, not provided by TMC2.

Original languageEnglish
Article number12124
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 14 Aug 2018

Fingerprint

Inner Auditory Hair Cells
Inner Ear
Proteins
Vestibular Hair Cells
Auditory Hair Cells
Cochlea

Bibliographical note

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Cite this

Asai, Yukako ; Pan, Bifeng ; Nist-Lund, Carl ; Galvin, Alice ; Lukashkin, Andrei N. ; Lukashkina, Victoria A. ; Chen, Tianwen ; Zhou, Wu ; Zhu, Hong ; Russell, Ian J. ; Holt, Jeffrey R. ; Géléoc, Gwenaelle S.G. / Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{ce8f5fd4b88d42f59df1a73add37e928,
title = "Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1",
abstract = "Recent work has demonstrated that transmembrane channel-like 1 protein (TMC1) is an essential component of the sensory transduction complex in hair cells of the inner ear. A closely related homolog, TMC2, is expressed transiently in the neonatal mouse cochlea and can enable sensory transduction in Tmc1-null mice during the first postnatal week. Both TMC1 and TMC2 are expressed at adult stages in mouse vestibular hair cells. The extent to which TMC1 and TMC2 can substitute for each other is unknown. Several biophysical differences between TMC1 and TMC2 suggest these proteins perform similar but not identical functions. To investigate these differences, and whether TMC2 can substitute for TMC1 in mature hair cells, we generated a knock-in mouse model allowing Cre-inducible expression of Tmc2. We assayed for changes in hair cell sensory transduction and auditory and vestibular function in Tmc2 knockin mice (Tm[Tmc2]) in the presence or absence of endogenous Tmc1, Tmc2 or both. Our results show that expression of Tm[TMC2] restores sensory transduction in vestibular hair cells and transiently in cochlear hair cells in the absence of TMC1. The cellular rescue leads to recovery of balance but not auditory function. We conclude that TMC1 provides some additional necessary function, not provided by TMC2.",
author = "Yukako Asai and Bifeng Pan and Carl Nist-Lund and Alice Galvin and Lukashkin, {Andrei N.} and Lukashkina, {Victoria A.} and Tianwen Chen and Wu Zhou and Hong Zhu and Russell, {Ian J.} and Holt, {Jeffrey R.} and G{\'e}l{\'e}oc, {Gwenaelle S.G.}",
note = "This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.",
year = "2018",
month = "8",
day = "14",
doi = "10.1038/s41598-018-28958-x",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
number = "1",

}

Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1. / Asai, Yukako; Pan, Bifeng; Nist-Lund, Carl; Galvin, Alice; Lukashkin, Andrei N.; Lukashkina, Victoria A.; Chen, Tianwen; Zhou, Wu; Zhu, Hong; Russell, Ian J.; Holt, Jeffrey R.; Géléoc, Gwenaelle S.G.

In: Scientific Reports, Vol. 8, No. 1, 12124, 14.08.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1

AU - Asai, Yukako

AU - Pan, Bifeng

AU - Nist-Lund, Carl

AU - Galvin, Alice

AU - Lukashkin, Andrei N.

AU - Lukashkina, Victoria A.

AU - Chen, Tianwen

AU - Zhou, Wu

AU - Zhu, Hong

AU - Russell, Ian J.

AU - Holt, Jeffrey R.

AU - Géléoc, Gwenaelle S.G.

N1 - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PY - 2018/8/14

Y1 - 2018/8/14

N2 - Recent work has demonstrated that transmembrane channel-like 1 protein (TMC1) is an essential component of the sensory transduction complex in hair cells of the inner ear. A closely related homolog, TMC2, is expressed transiently in the neonatal mouse cochlea and can enable sensory transduction in Tmc1-null mice during the first postnatal week. Both TMC1 and TMC2 are expressed at adult stages in mouse vestibular hair cells. The extent to which TMC1 and TMC2 can substitute for each other is unknown. Several biophysical differences between TMC1 and TMC2 suggest these proteins perform similar but not identical functions. To investigate these differences, and whether TMC2 can substitute for TMC1 in mature hair cells, we generated a knock-in mouse model allowing Cre-inducible expression of Tmc2. We assayed for changes in hair cell sensory transduction and auditory and vestibular function in Tmc2 knockin mice (Tm[Tmc2]) in the presence or absence of endogenous Tmc1, Tmc2 or both. Our results show that expression of Tm[TMC2] restores sensory transduction in vestibular hair cells and transiently in cochlear hair cells in the absence of TMC1. The cellular rescue leads to recovery of balance but not auditory function. We conclude that TMC1 provides some additional necessary function, not provided by TMC2.

AB - Recent work has demonstrated that transmembrane channel-like 1 protein (TMC1) is an essential component of the sensory transduction complex in hair cells of the inner ear. A closely related homolog, TMC2, is expressed transiently in the neonatal mouse cochlea and can enable sensory transduction in Tmc1-null mice during the first postnatal week. Both TMC1 and TMC2 are expressed at adult stages in mouse vestibular hair cells. The extent to which TMC1 and TMC2 can substitute for each other is unknown. Several biophysical differences between TMC1 and TMC2 suggest these proteins perform similar but not identical functions. To investigate these differences, and whether TMC2 can substitute for TMC1 in mature hair cells, we generated a knock-in mouse model allowing Cre-inducible expression of Tmc2. We assayed for changes in hair cell sensory transduction and auditory and vestibular function in Tmc2 knockin mice (Tm[Tmc2]) in the presence or absence of endogenous Tmc1, Tmc2 or both. Our results show that expression of Tm[TMC2] restores sensory transduction in vestibular hair cells and transiently in cochlear hair cells in the absence of TMC1. The cellular rescue leads to recovery of balance but not auditory function. We conclude that TMC1 provides some additional necessary function, not provided by TMC2.

UR - http://www.scopus.com/inward/record.url?scp=85053426417&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-28958-x

DO - 10.1038/s41598-018-28958-x

M3 - Article

VL - 8

JO - Scientific Reports

T2 - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 12124

ER -