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GRAIL基因淘汰赛小鼠可以防止与衰老相关的和噪音引起的听力损失

Kai-Fen Chuang¹, Chih-Hung Wang^1,2,3, Hang-Kang Chen¹

¹Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

Journal of the Chinese Medical Association : JCMA

|October 11, 2023

概括

与淋巴细胞 (GRAIL) 缺陷中的阳性相关的基因可以防止与年龄相关的和噪音引起的听力损失. GRAIL淘汰赛小鼠显示毛细胞和突触带损失减少,表明它在耳健康中起着保护作用.

科学领域:

耳鼻喉科耳鼻喉科耳鼻喉科
遗传学遗传学是一个
分子生物学分子生物学

背景情况:

听力损失是一个重要的全球健康问题,具有复杂的分子基础.
在耳发育和听力损失中涉及到的,是ubiquitin-proteasome系统.
与淋巴细胞 (GRAIL) 中的 anergy 相关的基因 E3 ubiquitin ligase 在与年龄相关的和噪音引起的听力损失中的作用以前没有被研究过.

研究的目的:

用小鼠模型研究GRAIL在与年龄相关和噪音引起的听力损失中的作用.
为了比较GRAIL缺乏对野生型 (WT) 和GRAIL淘汰赛 (KO) 小鼠的耳毛细胞和突触带的影响.

主要方法:

使用WT和GRAIL KO小鼠进行听觉脑干反应测试和对耳毛细胞和突触带的免疫光染色.
采用RNA测序来比较WT和KO小鼠在暴露于噪音后的基因表达模式,以确定潜在的致病点.

主要成果:

与WT小鼠相比,12个月后,GRAIL KO小鼠的听力值升高显著降低,耳部区域的外部毛细胞和突触带损失减少.
与WT小鼠相比,在暴露于噪音后,GRAIL KO小鼠的听力值升高显著降低,外皮毛细胞和突触带损失减少.
RNA测序揭示了CCL19,CCL21,IL25,GPX6和NOX1等基因在响应GRAIL缺陷背景下的噪音暴露时发生的显著变化.

结论:

格雷尔缺陷可以防止与衰老相关的听力损失和噪音引起的听力损失.
保护机制可能涉及突触调节,炎症和氧化应激通路,需要进一步调查.

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