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

研究成果: Article査読

11 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)626.e25-626.e34
ジャーナルNeurobiology of Aging
33
3
DOI
出版ステータスPublished - 03-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 加齢科学
  • 臨床神経学
  • 発生生物学
  • 老年医学

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