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 transduc...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7060bb4179c3426d8a8e22cd46477d42
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spelling	oai:doaj.org-article:7060bb4179c3426d8a8e22cd46477d422021-12-02T15:07:59ZTransgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc110.1038/s41598-018-28958-x2045-2322https://doaj.org/article/7060bb4179c3426d8a8e22cd46477d422018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28958-xhttps://doaj.org/toc/2045-2322Abstract 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.Yukako AsaiBifeng PanCarl Nist-LundAlice GalvinAndrei N. LukashkinVictoria A. LukashkinaTianwen ChenWu ZhouHong ZhuIan J. RussellJeffrey R. HoltGwenaelle S. G. GéléocNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1
description	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.
format	article
author	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
author_facet	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
author_sort	Yukako Asai
title	Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1
title_short	Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1
title_full	Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1
title_fullStr	Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1
title_full_unstemmed	Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1
title_sort	transgenic tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking tmc1
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7060bb4179c3426d8a8e22cd46477d42
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Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1

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