Cochlear Pathomorphogenesis of Incomplete Partition Type II in Slc26a4-Null Mice
Cochlear Pathomorphogenesis of Incomplete Partition Type II in Slc26a4-Null Mice
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DOI：
10.1007/s10162-021-00812-4
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发表时间：
2021-10-07
影响因子：
2.4
通讯作者：
Tsutsumi, Takeshi
中科院分区：
文献类型：
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作者：
Ito, Taku;Fujikawa, Taro;Tsutsumi, Takeshi
伴有SLC26A4突变的耳朵中常发现不完全分隔型II(IP-II)。具有IP-II的耳蜗体一般有11/2转；基转正常形成，顶转扩张或囊状。本研究的目的是研究SLC26A4基因缺失小鼠IP-II耳蜗病的病理形态发生机制。取SLC26A4(Delta/+)和SLC26A4(Delta/Delta)小鼠，分别于1日龄、8日龄、1月龄、3月龄解剖耳囊。用X射线微电子计算机断层扫描技术对样品进行成像。采用多平面切面和三维重建模型计算耳蜗管长度、耳蜗旋转角和蜗牛倾斜角。在膜迷路整装标本上计数内毛细胞数，测量耳蜗管长度。X光显微计算机断层扫描显示SLC26A4(Delta/Delta)小鼠由于鳞间隔膜的丢失或脱骨而导致囊性尖端转向，形态上类似于人类的IP-II。在SLC26A4(Delta/+)和SLC26A4(Delta/Delta)小鼠之间，垂直于蜗牛的平面显示出相似的平均旋转角度。相反，SLC26A4(Delta/Delta)小鼠的平均耳蜗管长度和平均内毛细胞数明显小于SLC26A4(Delta/+)小鼠。此外，蜗牛的平均倾斜角和平均宽度也有显著差异。我们对SLC26A4基因缺失小鼠的分析表明，IP-II在人类中反映了鳞间隔膜的丢失或脱骨，但并不是耳蜗转次数的减少。
Incomplete partition type II (IP-II) is frequently identified in ears with SLC26A4 mutations. Cochleae with IP-II are generally observed to have 11/2 turns; the basal turns are normally formed, and the apical turn is dilated or cystic. The objective of this study was to characterize the pathomorphogenesis of the IP-II cochlear anomaly in Slc26a4-null mice. Otic capsules were dissected from Slc26a4(Delta/+) and Slc26a4(Delta/Delta) mice at 1 and 8 days of age and at 1 and 3 months of age. X-ray micro-computed tomography was used to image samples. We used a multiplanar view and three-dimensional reconstructed models to calculate the cochlear duct length, cochlear turn rotation angle, and modiolus tilt angle. The number of inner hair cells was counted, and the length of the cochlear duct was measured in a whole-mount preparation of the membranous labyrinth. X-ray micro-computed tomography mid-modiolar planar views demonstrated cystic apical turns in Slc26a4(Delta/Delta) mice resulting from the loss or deossification of the interscalar septum, which morphologically resembles IP-II in humans. Planes vertical to the modiolus showed a similar mean rotation angle between Slc26a4(Delta/+) and Slc26a4(Delta/Delta) mice. In contrast, the mean cochlear duct length and mean number of inner hair cells in Slc26a4(Delta/Delta) mice were significantly smaller than in Slc26a4(Delta/+) mice. In addition, there were significant differences in the mean tilt angle and mean width of the modiolus. Our analysis of Slc26a4-null mice suggests that IP-II in humans reflects loss or deossification of the interscalar septum but not a decreased number of cochlear turns.