辛古林调节头发细胞皮质板形态,对人类和小鼠的听力有必要
Guang-Jie Zhu1,2,3, Yuhang Huang1,2, Linqing Zhang1,2
1State Key Laboratory of Pharmaceutical Biotechnology, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.
EMBO molecular medicine
|September 11, 2023
概括
辛古林 (CGN) 蛋白质缺乏导致自体主导非综合征性听力损失. 这项研究揭示了CGN.
科学领域:
- 遗传学和分子生物学
- 耳鼻喉科 耳鼻喉科 耳鼻喉科
- 细胞生物学 细胞生物学
背景情况:
- 辛古林 (CGN) 是细胞骨相关的蛋白质,位于上皮细胞的尖端结点.
- 它在发育和疾病中的生理作用在很大程度上是未知的.
- 自体主导非综合征性听力损失 (ADNSHL) 是一种常见的遗传性听力障碍.
研究的目的:
- 调查辛古林 (CGN) 在听力中的作用及其与ADNSHL的关联.
- 在一个多代家庭中确定听力损失的遗传原因.
主要方法:
- 一个ADNSHL.家族的遗传分析.
- 在人类和小鼠尾中分析CGN的表达.
- 产生和分析具有CGN突变 (Knockout和Knockin) 的小鼠模型.
- 在小鼠模型中评估毛发细胞结构和听觉功能.
主要成果:
- 在一个家族中与ADNSHL共分离的异构性CGN截断变体 (c.3330delG).
- 在Corti的器官中表达CGN,特别是在毛细胞中.
- 在小鼠中,CGN突变导致异常的毛细胞结构,受损的活性蛋白聚合和听力损失.
- 毛细胞特异性Cgn淘汰导致高频听力损失.
- 敲击小鼠的CGN突变表现出渐进的,对噪音敏感的听力损失和外皮毛细胞退化.
结论:
- 该CGN c.3330delG变种是ADNSHL的致病原体.
- CGN对于维持耳毛细胞结构和听觉功能至关重要.
- 缺少CGN会导致逐渐的听力损失和头发细胞退化.
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