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Study on a cause of hearing defect in Vlgr1 mutated mice

Vlgr1突变小鼠听力缺陷原因研究

基本信息

批准号：
17500227
负责人：
YAGI Hideshi
金额：
$ 2.24万
依托单位：
University of Fukui
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17500227/
关键词：
Vlgr1 knockout mice hearing defect cochlea hair cell stereocilium Vlgr1

项目摘要

1) Study on the functional domain of Vlgr1We collaborated on this theme with the group of French. We revealed that Vlgr1 was related to the proteins that consist of the ankle link of stereocilia.2) Study on the hearing defect of Vlgr1 knockout miceWe revealed that Vlgr1-knockout mice suffered from a hearing defect because of inner ear dysfunction, as indicated by auditory brainstem response and distortion product oto-acoustic emissions. The expression of Vlgr1 was identified in the developing hair cells from embryonic day 17 to postnatal day 10. Vlgr1 was localized in the base of stereocilia on hair cells using confocal microscopy. This Vlgr1 localization was limited to the base of stereocilia within approximately 200-400 nm from the apical surface of hair cells using immunoelectron microscopy. This localization of Vlgr1 was disappeared under the calcium free condition. Under the SEM studies, the Vlgr1 knockout mice showed malformation of the stereocilia of cochlear hair cells. At postnatal day 0, the appearance of hair bundles was almost normal in the Vlgr1 knockout mice. The cochlear hair bundles of Vlgr1 knockout mice became disarranged at postnatal day 8. Furthermore, the stereocilia in the Vlgr1 knockout mice became slanted and disarranged thereafter. These results indicate that loss of Vlgr1 resulted in abnormal development of stereocilia formation and the Vlgr1 was related to the formation of ankle link.

1)Vlgr1功能域的研究我们与法国的小组就这一主题进行了合作。2)对Vlgr1基因敲除小鼠听力缺陷的研究我们发现，Vlgr1基因敲除小鼠由于内耳功能障碍而出现听力缺陷，表现为听性脑干反应和失真产物耳声发射。从胚胎第17天到出生后第10天，Vlgr1在发育中的毛细胞中有表达。共聚焦显微镜下，Vlgr1定位于毛细胞的纤毛基底部。在免疫电子显微镜下，Vlgr1定位于距离毛细胞顶面约200-400 nm范围内的体毛纤毛底部。在无钙条件下，Vlgr1的这种定位消失。扫描电子显微镜观察发现，Vlgr1基因敲除小鼠耳蜗毛细胞的纤毛结构发生畸形。出生后第0天，Vlgr1基因敲除小鼠的毛束出现几乎是正常的。在出生后第8天，Vlgr1基因敲除小鼠的耳蜗毛束变得紊乱，此后，Vlgr1基因敲除小鼠的耳蜗毛纤毛变得倾斜和紊乱。这些结果表明，Vlgr1基因的缺失导致了立体纤毛形成的异常发育，Vlgr1基因与踝关节的形成有关。