Altered traveling wave propagation and reduced endocochlear potential associated with cochlear dysplasia in the BETA2/NeuroD1 null mouse.

Altered traveling wave propagation and reduced endocochlear potential associated with cochlear dysplasia in the BETA2/NeuroD1 null mouse.
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BETA2/NeuroD1 缺失小鼠中与耳蜗发育不良相关的行波传播改变和耳蜗电位降低。

DOI:
10.1007/s10162-007-0092-9
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发表时间:
2007
期刊:
Journal of the Association for Research in Otolaryngology : JARO
影响因子:
--
通讯作者:
Oghalai,JohnS
Oghalai,JohnS
中科院分区:
--
文献类型:
--
作者:
Xia,Anping;Visosky,AnnMarieB;Cho,Jang-Hyeon;Tsai,Ming-Jer;Pereira,FredA;Oghalai,JohnS

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BETA2/NeuroD 1基因敲除小鼠存在耳蜗发育不良。它的耳蜗管比正常人短,缺乏螺旋神经节神经元,毛细胞紊乱。我们用激光多普勒振动仪测量了镫骨机械刺激时,切除耳蜗中覆盖膜在声频下的垂直运动。虽然野生型,杂合子和无效小鼠之间的调谐曲线的锐度是相似的基础上,无效突变体有更广泛的调谐在顶点。在基地和顶点,空小鼠有较少的相位滞后积累与增加刺激频率比野生型或杂合子小鼠。在体研究表明,null小鼠缺乏畸变产物耳声发射,耳蜗微音和耳蜗内电位被发现严重降低。可以诱发电诱发耳声发射,尽管幅度低于野生型小鼠。耳蜗横截面显示一个不完整的分区畸形,与开窗内的蜗轴连接的耳蜗转弯。来自无效小鼠的外毛细胞在其侧壁内表现出正常的普雷斯廷表达模式和正常的FM 1-43染料进入。总的来说,这些数据表明,虽然耳蜗发育不良可能存在音调性,但行波传播异常快。此外,电诱发耳声发射的存在表明,外毛细胞反向转导存在,虽然在耳蜗力学的改变的声学响应的形状。
The BETA2/NeuroD1 null mouse has cochlear dysplasia. Its cochlear duct is shorter than normal, there is a lack of spiral ganglion neurons, and there is hair cell disorganization. We measured vertical movements of the tectorial membrane at acoustic frequencies in excised cochleae in response to mechanical stimulation of the stapes using laser doppler vibrometry. While tuning curve sharpness was similar between wild-type, heterozygotes, and null mice in the base, null mutants had broader tuning in the apex. At both the base and the apex, null mice had less phase lag accumulation with increasing stimulus frequency than wild-type or heterozygote mice. In vivo studies demonstrated that the null mouse lacked distortion product otoacoustic emissions, and the cochlear microphonic and endocochlear potential were found to be severely reduced. Electrically evoked otoacoustic emissions could be elicited, although the amplitudes were lower than those of wild-type mice. Cochlear cross-sections revealed an incomplete partition malformation, with fenestrations within the modiolus that connected the cochlear turns. Outer hair cells from null mice demonstrated the normal pattern of prestin expression within their lateral walls and normal FM 1-43 dye entry. Overall, these data demonstrate that while tonotopicity can exist with cochlear dysplasia, traveling wave propagation is abnormally fast. Additionally, the presence of electrically evoked otoacoustic emissions suggests that outer hair cell reverse transduction is present, although the acoustic response is shaped by the alterations in cochlear mechanics.
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DOI: --
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期刊:
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