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. 2021 May 28;118(22):e2019681118. doi: 10.1073/pnas.2019681118

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Copyright © 2021 the Author(s). Published by PNAS.

This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

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Fig. 5. — Tmem43-p.(Arg372Ter) KI mice display morphological and physiological dysfunction. (A) Confocal micrographs of the organs of Corti from 1-mo-old littermates of Tmem43^+/+, Tmem43^+/KI, and Tmem43^KI/KI. Three-dimensional rendered images were obtained from the apical turn of cochlea immunolabeled with anti-TMEM43 (red, first row) and anti-calretinin (green, second row). XZ and ZY section views are shown (third row). Surface object clipping images of a single IHC (fourth row, Left) and cut-away object images of the same IHC (fourth row, Right) are shown. Cut-away plane is parallel to the cuticular plate. (B) sEM findings at the level of reticular lamina of hair cells. Yellow and cyan dotted lines each indicate apical surface area of inner border cells of Tmem43^+/+ and Tmem43^+/KI, respectively. (C) Summary graphs of apical surface area of inner border cells (n = 50) from B. (D) Representative sEM images of whole mounts from apical turns of cochlea showing intact OHC bundles in Tmem43^+/KI mice that are comparable to Tmem43^+/+. (E) Representative ABR waveforms in response to 16 kHz tone burst sound that are recorded longitudinally at time intervals from the same mice in each genotype. y-axis, sound pressure level (SPL). (F) Mean ± SEM. ABR thresholds from littermate Tmem43^+/+ (n = 10), Tmem43^+/KI (n = 10), and Tmem43^KI/KI (n = 10) at 3 mo. (G) Mean ± SEM. ABR thresholds from littermate Tmem43^+/+ (n = 3), Tmem43^+/KI (n = 12), and Tmem43^KI/KI (n = 3) measured at 6 mo. (H) Mean ± SEM. ABR thresholds from littermate Tmem43^+/+ (n = 3), Tmem43^+/KI (n = 3), and Tmem43^KI/KI (n = 3) measured at 11 mo. (I) Mean ± SEM growth functions of DPOAE thresholds from 4 to 32 kHz for littermate Tmem43^+/+ (n = 6) and Tmem43^+/KI (n = 6) measured at 3 mo. (J) Mean ± SEM growth functions of DPOAE thresholds from 4 to 32 kHz for littermate Tmem43^+/+ (n = 8) and Tmem43^+/KI (n = 8) measured at 6 mo. The DPOAE responses from Tmem43^+/KI are not significantly different from Tmem43^+/+ (ANOVA, P > 0.05) at whole kHz and significantly higher than noise level (yellow) at the frequencies from 8 to 19 kHz.