Fu Xiaolong, Zhang Linqing, Jin Yecheng, Sun Xiaoyang, Zhang Aizhen, Wen Zongzhuang, Zhou Yichen, Xia Ming, Gao Jiangang
School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
Department of Otolaryngology-Head and Neck Surgery, The Second Hospital of Shandong University, Jinan 250033, China.
Neural Plast. 2016;2016:6720420. doi: 10.1155/2016/6720420. Epub 2016 Dec 22.
MYH14 is a member of the myosin family, which has been implicated in many motile processes such as ion-channel gating, organelle translocation, and the cytoskeleton rearrangement. Mutations in MYH14 lead to a DFNA4-type hearing impairment. Further evidence also shows that MYH14 is a candidate noise-induced hearing loss (NIHL) susceptible gene. However, the specific roles of MYH14 in auditory function and NIHL are not fully understood. In the present study, we used CRISPR/Cas9 technology to establish a Myh14 knockout mice line in CBA/CaJ background (now referred to as Myh14 mice) and clarify the role of MYH14 in the cochlea and NIHL. We found that Myh14 mice did not exhibit significant hearing loss until five months of age. In addition, Myh14 mice were more vulnerable to high intensity noise compared to control mice. More significant outer hair cell loss was observed in Myh14 mice than in wild type controls after acoustic trauma. Our findings suggest that Myh14 may play a beneficial role in the protection of the cochlea after acoustic overstimulation in CBA/CaJ mice.
MYH14是肌球蛋白家族的成员,该家族与许多运动过程有关,如离子通道门控、细胞器转运和细胞骨架重排。MYH14突变会导致DFNA4型听力障碍。进一步的证据还表明,MYH14是噪声性听力损失(NIHL)的易感基因。然而,MYH14在听觉功能和NIHL中的具体作用尚未完全明确。在本研究中,我们使用CRISPR/Cas9技术在CBA/CaJ背景下建立了Myh14基因敲除小鼠品系(现称为Myh14小鼠),并阐明了MYH14在耳蜗和NIHL中的作用。我们发现,Myh14小鼠直到五个月大时才表现出明显的听力损失。此外,与对照小鼠相比,Myh14小鼠对高强度噪声更敏感。声学创伤后,Myh14小鼠的外毛细胞损失比野生型对照更明显。我们的研究结果表明,在CBA/CaJ小鼠中,Myh14可能在声学过度刺激后对耳蜗的保护中发挥有益作用。