• Hiroyuki Konishi, Nobutaka Ohgami, Aika Matsushita, Yuki Kondo, Yuki Aoyama, Masaaki Kobayashi, Taku Nagai, Shinya Ugawa, Kiyofumi Yamada, Masashi Kato, and Hiroshi Kiyama.
• Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. Electronic address: konishi@med.nagoya-u.ac.jp.
• Neuroscience. 2017 May 20; 351: 15-23.

AbstractDiphtheria toxin (DT) administration into transgenic mice that express the DT receptor (DTR) under control of specific promoters is often used for cell ablation studies in vivo. Because DTR is not expressed in mice, DT injection has been assumed to be nontoxic to cells in vivo. In this study, we demonstrated that DT application during the juvenile stage leads to hearing loss in wild-type mice. Auditory brainstem response measurement showed severe hearing loss in C57BL/6 mice administered DT during the juvenile period, and the hearing loss persisted into adulthood. However, ototoxicity did not occur when DT was applied on postnatal day 28 or later. Histological studies demonstrated that hearing loss was accompanied by significant degeneration of inner and outer hair cells (HCs), as well as spiral ganglion neurons. Scanning electron microscopy showed quick degeneration of inner HCs within 3days and gradual degeneration of outer HCs within 1week. These results demonstrated that DT has ototoxic action on C57BL/6 mice during the juvenile period, but not thereafter, and the hearing loss was due to degeneration of inner and outer HCs by unknown DT-related mechanisms.Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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