Gao Jiangang, Maison Stéphane F, Wu Xudong, Hirose Keiko, Jones Sherri M, Bayazitov Ildar, Tian Yong, Mittleman Guy, Matthews Douglas B, Zakharenko Stanislav S, Liberman M Charles, Zuo Jian
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Mol Cell Biol. 2007 Jun;27(12):4500-12. doi: 10.1128/MCB.02051-06. Epub 2007 Apr 16.
The function of the orphan glutamate receptor delta subunits (GluRdelta1 and GluRdelta2) remains unclear. GluRdelta2 is expressed exclusively in the Purkinje cells of the cerebellum, and GluRdelta1 is prominently expressed in inner ear hair cells and neurons of the hippocampus. We found that mice lacking the GluRdelta1 protein displayed significant cochlear threshold shifts for frequencies of >16 kHz. These deficits correlated with a substantial loss of type IV spiral ligament fibrocytes and a significant reduction of endolymphatic potential in high-frequency cochlear regions. Vulnerability to acoustic injury was significantly enhanced; however, the efferent innervation of hair cells and the classic efferent inhibition of outer hair cells were unaffected. Hippocampal and vestibular morphology and function were normal. Our findings show that the orphan GluRdelta1 plays an essential role in high-frequency hearing and ionic homeostasis in the basal cochlea, and the locus encoding GluRdelta1 represents a candidate gene for congenital or acquired high-frequency hearing loss in humans.
孤儿谷氨酸受体δ亚基（GluRδ1和GluRδ2）的功能仍不清楚。GluRδ2仅在小脑的浦肯野细胞中表达，而GluRδ1在海马体的内耳毛细胞和神经元中显著表达。我们发现，缺乏GluRδ1蛋白的小鼠在频率大于16kHz时表现出明显的耳蜗阈值偏移。这些缺陷与IV型螺旋韧带纤维细胞的大量丧失以及高频耳蜗区域内淋巴电位的显著降低相关。对声学损伤的易感性显著增强；然而，毛细胞的传出神经支配和外毛细胞的经典传出抑制未受影响。海马体和前庭的形态及功能正常。我们的研究结果表明，孤儿GluRδ1在耳蜗基部的高频听力和离子稳态中起重要作用，编码GluRδ1的位点代表人类先天性或后天性高频听力损失的一个候选基因。
