Partial impairment of c-Ret at tyrosine 1062 accelerates age-related hearing loss in mice

Nobutaka Ohgami, Michiru Ida-Eto, Naomi Sakashita, Michihiko Sone, Tsutomu Nakashima, Keiji Tabuchi, Tomofumi Hoshino, Atsuyoshi Shimada, Toyonori Tsuzuki, Masahiko Yamamoto, Gen Sobue, Mayumi Jijiwa, Naoya Asai, Akira Hara, Masahide Takahashi, Masashi Kato

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10 Citations (Scopus)

Abstract

c-Ret has been shown to be crucial for neural development and survival. We have recently shown that complete impairment of tyrosine 1062 (Y1062)-phosphorylation in c-Ret causes congenital hearing loss with neurodegeneration of spiral ganglion neurons (SGNs) in homozygous c-Ret knockin mice (c-Ret-KIY1062F/Y1062F-mice). However, there is no information to link c-Ret and age-related hearing loss. Here we show that partial impairment of Y1062-phosphorylation in c-Ret accelerates age-related hearing loss in heterozygous c-Ret Y1062F knockin mice (c-Ret-KIY1062F/+-mice). In contrast, complete impairment of serine 697 (S697)-phosphorylation in c-Ret did not affect hearing levels in 10-month-old homozygous c-Ret S697A knockin mice (c-Ret-KIS697A/S697A-mice). The hearing loss involved late-onset neurodegeneration of spiral ganglion neurons in c-Ret-KIY1062F/+-mice. Morphological abnormalities in inner- and outer-hair cells and the stria vascularis in c-Ret-KIY1062F/+-mice were undetectable. The acceleration of age-related hearing loss in c-Ret-KIY1062F/+-mice was rescued by introducing constitutively activated RET. Thus, our results suggest that c-Ret is a novel age-related hearing loss-related molecule in mice. Our results suggest that these hearing losses partially share a common pathogenesis that is monogenetically caused by a single point mutation (Y1062F) in c-Ret.

Original languageEnglish
Pages (from-to)626.e25-626.e34
JournalNeurobiology of Aging
Volume33
Issue number3
DOIs
Publication statusPublished - 03-2012

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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    Ohgami, N., Ida-Eto, M., Sakashita, N., Sone, M., Nakashima, T., Tabuchi, K., Hoshino, T., Shimada, A., Tsuzuki, T., Yamamoto, M., Sobue, G., Jijiwa, M., Asai, N., Hara, A., Takahashi, M., & Kato, M. (2012). Partial impairment of c-Ret at tyrosine 1062 accelerates age-related hearing loss in mice. Neurobiology of Aging, 33(3), 626.e25-626.e34. https://doi.org/10.1016/j.neurobiolaging.2011.04.002