2019 Fiscal Year Final Research Report
Abnormality of programmed cell death and treatment in connexin26 mutation deafness model mouse
| Project/Area Number |
17K16946
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 先天性難聴 / コネキシン遺伝子 / Gjb2 / プログラム細胞死 / 内耳コルチ器 |
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| Outline of Final Research Achievements |
The greater epithelial ridge (GER) is a developmental structure in the maturation of the organ of Corti. Situated near the inner hair cells of neonatal mice, the GER undergoes a wave of apoptosis after postnatal day 8 (P8). We evaluated the GER at P8 and P12 in human gap junction protein, beta 2, 26 kDa (GJB2) (also known as connexin 26 or CX26). In both non-transgenic (non-Tg) and R75W +mice, some GER cells exhibited apoptotic characteristics at P8. In R75W+mice at P12, apoptotic cells were still clearly evident in the GER. In R75W +mice, therefore, apoptosis in the GER persisted until a later stage of cochlear development. Cultured cells expressing CX26-R75W revealed that the mutation affects the biochemical properties of gap binding (Kamiya et al. in preparation). The fertilized eggs of R75W +mice have been selected by breeding and genotyping to create a model of deafness for analysis.
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| Free Research Field |
耳鼻咽喉科学
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| Academic Significance and Societal Importance of the Research Achievements |
GJB2の優性変異R75Wを導入したトランスジェニックマウスの8日齢と12日齢では、正常発達に起こるアポトーシスによるプログラム細胞死が遅延し、一時的にコルチ器が過形成の状態になることが示された。特にコルチ器近傍のGERにおいて顕著で、このためコルチ器の圧排が生じ、有毛細胞の機能低下とコルチトンネルの消失の原因となることが示唆された。以上より、GJB2変異型難聴ではGER領域のプログラム細胞死が遅延しているためコルチ器形成が異常となり、聴覚受容機能の低下の一因となる新たな病態の可能性が示唆された。今後はGER領域の遺伝子発現解析でのCX26-R75W変異による発生への影響を解析予定である。
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