Failure of fluid absorption in the endolymphatic sac initiates cochlear enlargement that leads to deafness in mice lacking pendrin expression.
Failure of fluid absorption in the endolymphatic sac initiates cochlear enlargement that leads to deafness in mice lacking pendrin expression.
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DOI：
10.1371/journal.pone.0014041
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发表时间：
2010-11-17
期刊：
影响因子：
3.7
通讯作者：
Wangemann P
中科院分区：
文献类型：
--
作者：
Kim HM;Wangemann P
SLC26A4基因突变是遗传性耳聋最常见的原因之一。相应小鼠模型Slc26a4−/−的耳聋是由耳蜗腔异常增大引起的。本研究的目的是确定耳蜗肿大是由耳蜗液体运输缺陷引起的，还是由连接的腔室（前庭迷路和内淋巴囊）液体运输功能障碍引起的。Slc26a4+/−和Slc26a4−/−小鼠的胚胎内耳在离体或器官培养2天后用共聚焦显微镜检查。培养允许观察完整的、结扎的或部分切除的内耳。耳蜗腔的形成在胚胎日(E) 13.5至14.5之间开始于耳蜗底部。与Slc26a4+/−小鼠相比，Slc26a4−/−小鼠立即明显增大。在Slc26a4+/ -和Slc26a4 - / -小鼠中，在E14.5结扎耳蜗与前庭迷路分离导致耳蜗腔缩小。在E14.5切除内淋巴囊会导致Slc26a4+/ -小鼠的耳蜗腔增大，但不会导致Slc26a4 - / -小鼠已经增大的耳蜗腔进一步增大。结扎或切除后，在E17.5，没有改变耳蜗腔。综上所述，这些数据表明耳蜗腔的形成是由前庭迷路的液体分泌引起的，并由内淋巴囊的液体吸收暂时控制。由于缺乏Slc26a4的表达，内淋巴囊液体吸收的失败似乎会在缺乏Slc26a4功能性表达的小鼠（也可能是人类）中引发耳蜗增大。
Mutations of SLC26A4 are among the most prevalent causes of hereditary deafness. Deafness in the corresponding mouse model, Slc26a4−/−, results from an abnormally enlarged cochlear lumen. The goal of this study was to determine whether the cochlear enlargement originates with defective cochlear fluid transport or with a malfunction of fluid transport in the connected compartments, which are the vestibular labyrinth and the endolymphatic sac. Embryonic inner ears from Slc26a4+/− and Slc26a4−/− mice were examined by confocal microscopy ex vivo or after 2 days of organ culture. Culture allowed observations of intact, ligated or partially resected inner ears. Cochlear lumen formation was found to begin at the base of the cochlea between embryonic day (E) 13.5 and 14.5. Enlargement was immediately evident in Slc26a4−/− compared to Slc26a4+/− mice. In Slc26a4+/− and Slc26a4−/− mice, separation of the cochlea from the vestibular labyrinth by ligation at E14.5 resulted in a reduced cochlear lumen. Resection of the endolymphatic sacs at E14.5 led to an enlarged cochlear lumen in Slc26a4+/− mice but caused no further enlargement of the already enlarged cochlear lumen in Slc26a4−/− mice. Ligation or resection performed later, at E17.5, did not alter the cochlea lumen. In conclusion, the data suggest that cochlear lumen formation is initiated by fluid secretion in the vestibular labyrinth and temporarily controlled by fluid absorption in the endolymphatic sac. Failure of fluid absorption in the endolymphatic sac due to lack of Slc26a4 expression appears to initiate cochlear enlargement in mice, and possibly humans, lacking functional Slc26a4 expression.
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影响因子：
2.5
作者：
Lelli, Andrea;Asai, Yukako;Geleoc, Gwenaeelle S. G.
通讯作者：
Geleoc, Gwenaeelle S. G.
影响因子：
25
作者：
Géléoc, GSG;Holt, JR
通讯作者：
Holt, JR
DOI：
10.1007/s10162-002-3052-4
发表时间：
2003-09-01
影响因子：
2.4
作者：
Royaux, IE;Belyantseva, IA;Green, ED
通讯作者：
Green, ED
影响因子：
1.4
作者：
KIMURA, RS
通讯作者：
KIMURA, RS
影响因子：
4.8
作者：
Ng, Lily;Hernandez, Arturo;Forrest, Douglas
通讯作者：
Forrest, Douglas