Apoptosis of type I spiral ganglion neuron cells in Otof-mutant mice

Nobuyoshi Tsuzuki, Kazunori Namba, Chika Saegusa, Hideki Mutai, Takanori Nishiyama, Naoki Oishi, Tatsuo Matsunaga, Masato Fujioka, Hiroyuki Ozawa

Research output: Contribution to journalArticlepeer-review


Otof, which encodes otoferlin, knockout mice are considered model mice for auditory neuropathy spectrum disorder, which is characterized by an absent auditory brainstem response (ABR) despite preserved distortion product otoacoustic emission (DPOAE). Although otoferlin-deficient mice lack neurotransmitter release at the inner hair cell (IHC) synapse, it remains unclear how the Otof mutation affects spiral ganglions. Thus, we used Otof-mutant mice carrying the Otoftm1a(KOMP)Wtsi allele (Otoftm1a) and analyzed spiral ganglion neurons (SGNs) in Otoftm1a/tm1a mice by immunolabeling type Ⅰ SGNs (SGN-Ⅰ) and type II SGNs (SGN-II). We also examined apoptotic cells in SGNs. Four-week-old Otoftm1a/tm1a mice had an absent ABR but normal DPOAEs. The number of SGNs was significantly lower in Otoftm1a/tm1a mice on postnatal day 7 (P7), P14, and P28 compared with that of wild-type mice. Moreover, significantly more apoptotic SGNs were observed in Otoftm1a/tm1a mice than in wild-type mice on P7, P14, and P28. SGN-IIs were not significantly reduced in Otoftm1a/tm1a mice on P7, P14, and P28. No apoptotic SGN-IIs were observed under our experimental conditions. In summary, Otoftm1a/tm1a mice showed a reduction in SGNs accompanied by apoptosis of SGN-Ⅰs even before the onset of hearing. We speculate that the reduction in SGNs with apoptosis is a secondary defect caused by a lack of otoferlin in IHCs. Appropriate glutamatergic synaptic inputs may be important for the survival of SGNs.

Original languageEnglish
Article number137178
JournalNeuroscience Letters
Publication statusPublished - 2023 Apr 23


  • Apoptosis
  • Auditory neuropathy spectrum disorder
  • Inner hair cell
  • OTOF
  • Otoferlin
  • Spiral ganglion neurons

ASJC Scopus subject areas

  • Neuroscience(all)


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