Downregulation of otospiralin, a novel inner ear protein, causes hair cell degeneration and deafness

被引:29
作者
Delprat, B
Boulanger, A
Wang, J
Beaudoin, V
Guitton, MJ
Ventéo, S
Dechesne, CJ
Pujol, R
Lavigne-Rebillard, M
Puel, JL
Hamel, CP
机构
[1] INSERM, U254, Lab Neurobiol Audit, F-34090 Montpellier, France
[2] Univ Quebec Trois Rivieres, Dept Chim Biol, Trois Rivieres, PQ G9A 5H7, Canada
[3] Univ Montpellier 2, INSERM, U432, F-34095 Montpellier 05, France
关键词
otospiralin; cochlea; vestibule; hair cell; deafness; gene; antisense; inner ear;
D O I
10.1523/JNEUROSCI.22-05-01718.2002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Mesenchymal nonsensory regions of the inner ear are important structures surrounding the neurosensory epithelium that are believed to participate in the ionic homeostasis of the cochlea and vestibule. We report here the discovery of otospiralin, an inner ear-specific protein that is produced by fibrocytes from these regions, including the spiral ligament and spiral limbus in the cochlea and the maculae and semicircular canals in the vestibule. Otospiralin is a novel 6.4 kDa protein of unknown function that shares a protein motif with the gag p30 core shell nucleocapsid protein of type C retroviruses. To evaluate its functional importance, we downregulated otospiralin by cochlear perfusion of antisense oligonucleotides in guinea pigs. This led to a rapid threshold elevation of the compound action potentials and irreversible deafness. Cochlear examination by transmission electron microscopy revealed hair cell loss and degeneration of the organ of Corti. This demonstrates that otospiralin is essential for the survival of the neurosensory epithelium.
引用
收藏
页码:1718 / 1725
页数:8
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