C-Ret-mediated hearing loss in mice with Hirschsprung disease

Nobutaka Ohgami, Michiru Ida-Eto, Takashi Shimotake, 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: ジャーナルへの寄稿学術論文査読

56 被引用数 (Scopus)

抄録

A significantly increased risk for dominant sensorineural deafness in patients who have Hirschsprung disease (HSCR) caused by endothelin receptor type B and SOX10 has been reported. Despite the fact that c-RET is the most frequent causal gene of HSCR, it has not been determined whether impairments of c-Ret and c-RET cause congenital deafness in mice and humans. Here, we show that impaired phosphorylation of c-Ret at tyrosine 1062 causes HSCR-linked syndromic congenital deafness in c-Ret knockin (KI) mice. The deafness involves neurodegeneration of spiral ganglion neurons (SGNs) with not only impaired phosphorylation of Akt and NF-κB but decreased expression of calbindin D28k in inner ears. The congenital deafness involving neurodegeneration of SGNs in c-Ret KI mice was rescued by introducing constitutively activated RET. Taken together with our results for three patients with congenital deafness with c-RET-mediated severe HSCR, our results indicate that c-Ret and c-RET are a deafness-related molecule in mice and humans.

本文言語英語
ページ(範囲)13051-13056
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
107
29
DOI
出版ステータス出版済み - 20-07-2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • 一般

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