Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1.
Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function in mice lacking Tmc1.
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DOI：
10.1038/s41598-018-28958-x
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发表时间：
2018-08-14
影响因子：
4.6
通讯作者：
Géléoc GSG
中科院分区：
文献类型：
--
作者：
Asai Y;Pan B;Nist-Lund C;Galvin A;Lukashkin AN;Lukashkina VA;Chen T;Zhou W;Zhu H;Russell IJ;Holt JR;Géléoc GSG
最近的工作表明，跨膜通道样蛋白1（TMC 1）是内耳毛细胞感觉转导复合体的重要组成部分。一个密切相关的同源物，TMC 2，在新生小鼠耳蜗中瞬时表达，并能在出生后第一周内使Tmc 1基因缺失小鼠的感觉转导。TMC1和TMC2在成年小鼠前庭毛细胞中表达。TMC 1和TMC 2可以相互替代的程度尚不清楚。TMC 1和TMC 2之间的一些生物物理差异表明这些蛋白质执行相似但不相同的功能。为了研究这些差异，以及TMC2是否可以在成熟毛细胞中取代TMC1，我们产生了允许Cre诱导表达Tmc 2的敲入小鼠模型。我们检测了Tmc 2基因敲入小鼠（Tm[Tmc 2]）在存在或不存在内源性Tmc 1、Tmc 2或两者的情况下毛细胞感觉转导以及听觉和前庭功能的变化。我们的研究结果表明，Tm[TMC 2]的表达恢复前庭毛细胞的感觉转导，并在没有TMC 1的耳蜗毛细胞短暂。细胞拯救导致平衡的恢复，但不是听觉功能。我们的结论是，TMC 1提供了一些额外的必要功能，而不是由TMC 2提供。
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.
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影响因子：
2.5
作者：
Lelli, Andrea;Asai, Yukako;Geleoc, Gwenaeelle S. G.
通讯作者：
Geleoc, Gwenaeelle S. G.
影响因子：
16.6
作者：
Giese APJ;Tang YQ;Sinha GP;Bowl MR;Goldring AC;Parker A;Freeman MJ;Brown SDM;Riazuddin S;Fettiplace R;Schafer WR;Frolenkov GI;Ahmed ZM
通讯作者：
Ahmed ZM
影响因子：
30.8
作者：
Kurima, K;Peters, LM;Griffith, AJ
通讯作者：
Griffith, AJ
DOI：
10.1073/pnas.0604883103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Kafri, Ran;Levy, Melissa;Pilpel, Yitzhak
通讯作者：
Pilpel, Yitzhak
影响因子：
15.9
作者：
Kawashima, Yoshiyuki;Geleoc, Gwenaelle S. G.;Griffith, Andrew J.
通讯作者：
Griffith, Andrew J.