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Cochlear Pathomorphogenesis of Incomplete Partition Type II in Slc26a4-Null Mice


Incomplete partition type II (IP-II) is frequently identified in ears with SLC26A4 mutations. Cochleae with IP-II are generally observed to have 1½ 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 Slc26a4Δ/+ and Slc26a4Δ/Δ 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 Slc26a4Δ/Δ 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 Slc26a4Δ/+ and Slc26a4Δ/Δ mice. In contrast, the mean cochlear duct length and mean number of inner hair cells in Slc26a4Δ/Δ mice were significantly smaller than in Slc26a4Δ/+ 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.

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Supported by a Grant-in-Aid for Scientific Research (grant No. 17K11316, 17K11314) from the Ministry of Health, Labor, and Welfare of Japan, NIDCD intramural research fund Z01-DC-000060, and a research grant from Kao Melanin Workshop.

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T.I. designed the research, performed the experiments, analyzed the data, and wrote the manuscript. T.F., K.H., and A.M. performed the experiments. H.W., J.B., Y. K., and T. M. provided critical feedback. A.G. and T.T. helped guide the research, analysis, and manuscript. All of the authors read and critically reviewed the manuscript.

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Correspondence to Taku Ito.

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All procedures involving animals were approved by the Institutional Animal Care and Use Committee of Tokyo Medical and Dental University (No. A2019-280A).

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Ito, T., Fujikawa, T., Honda, K. et al. Cochlear Pathomorphogenesis of Incomplete Partition Type II in Slc26a4-Null Mice. JARO 22, 681–691 (2021).

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  • Slc26a4
  • Micro-CT
  • Incomplete partition type II
  • Mondini deformity
  • Modiolus