Exposure to diphtheria toxin during the juvenile period impairs both inner and outer hair cells in C57BL/6 mice

Hiroyuki Konishi, Nobutaka Ohgami, Aika Matsushita, Yuki Kondo, Yuki Aoyama, Masaaki Kobayashi, Taku Nagai, Shinya Ugawa, Kiyofumi Yamada, Masashi Kato, Hiroshi Kiyama

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Diphtheria 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 3 days and gradual degeneration of outer HCs within 1 week. 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.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalNeuroscience
Volume351
DOIs
Publication statusPublished - 20-05-2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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