Hearing threshold elevation precedes hair-cell loss in prestin knockout mice
Hearing threshold elevation precedes hair-cell loss in prestin knockout mice
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DOI：
10.1016/j.molbrainres.2004.03.020
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发表时间：
2004-07-05
期刊：
影响因子：
--
通讯作者：
Zuo, J
中科院分区：
文献类型：
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作者：
Wu, XD;Gao, JG;Zuo, J
我们先前对普雷斯廷基因敲除小鼠的研究表明，普雷斯廷是外毛细胞（OHC）和耳蜗放大器的电活动所必需的。由于在成年普雷斯廷-/-小鼠耳蜗基底25%处观察到毛细胞损失，因此尚不清楚毛细胞损失如何进展，听力阈值是否升高，以及年轻普雷斯廷-/-小鼠的OHC是否具有正常的超微结构。我们在这里报告说，在普雷斯廷-/-小鼠，没有显着的毛细胞损失发生在出生后第28天（P28），毛细胞凋亡开始于P28，和损失的内毛细胞落后于OHC。早在P14，普雷斯廷-/-小鼠的听力阈值显著升高（约25 dB）;在P21，它们在高频下的阈值显著升高（约50 dB）。普雷斯廷杂合（+/-）小鼠在P21时显示出显著的阈值升高（约3.5 dB）。透射电镜观察外毛细胞的中柱体、侧壁、紧密连接和突触未见明显异常。我们的研究结果表明，普雷斯廷的缺乏，而不是毛细胞的损失，是高频听阈升高的主要原因在普雷斯廷-/-和+/-小鼠。(C)2004 Elsevier B. V.保留所有权利。
Our previous characterization of prestin knockout (-/-) mice demonstrated that prestin is required for the eletromotility of outer hair cells (OHCs) and for the cochlear amplifier. Because hair-cell loss was observed in the basal 25% of cochleae in adult prestin-/- mice, it remained unclear how hair-cell loss progressed, whether hearing thresholds were elevated, and whether OHCs had normal ultra-structure in young prestin-/- mice. We report here that in prestin-/- mice, no significant hair-cell loss occurred before postnatal day 28 (P28); apoptosis of hair cells began at P28; and the loss of inner hair cells lagged behind that of OHCs. The prestin -/- mice had hearing thresholds that were significantly elevated (by approximately 25 dB) as early as P 14; their thresholds at high frequencies were significantly elevated (by approximately 50 dB) at P21. The prestin heterozygous (+/-) mice displayed a significant threshold elevation (approximately 3.5 dB) at P21. In addition, transmission electronic microscopy shown that no obvious abnormality occurs in the sterocilla, lateral wall, tight junction and synapses of the outer hair cells. Our results demonstrate that the absence of prestin, not hair-cell loss, is the primary cause of high-frequency hearing threshold elevation in prestin-/- and +/- mice. (C) 2004 Elsevier B.V. All rights reserved.