Tprn is essential for the integrity of stereociliary rootlet in cochlear hair cells in mice  

作　　者：Yuqin Men Xiujuan Li Hailong Tu Aizhen Zhang Xiaolong Fu Zhishuo Wang Yecheng Jin Congzhe Hou Tingting Zhang Sen Zhang Yichen Zhou Boqin Li Jianfeng Li Xiaoyang Sun Haibo Wang Jiangang Gao 

机构地区：[1]School of Life Science,Shandong University,Jinan 250100,China [2]Rizhao Polytechnic,Rizhao 276826,China [3]The Second Hospital of Shandong University,Jinan 250033,China [4]Electron Microscopy Laboratory,Shandong Institute of Otolaryngology,Jinan 250022,China [5]Laboratory of Electron Microscopy,Jinan WEI-YA Biotech Company,Jinan 250100,China [6]Department of Otolaryngology-Head and Neck Surgery,Provincial Hospital Affiliated to Shandong University,Jinan 250021,China

出　　处：《Frontiers of Medicine》2019年第6期690-704,共15页医学前沿（英文版）

摘　　要：Tprn encodes the taperin protein,which is concentrated in the tapered region of hair cell stereocilia in the inner ear.In humans,TPRN mutations cause autosomal recessive nonsyndromic deafness(DFNB79)by an unknown mechanism.To determine the role of Tprn in hearing,we generated Tprn-null mice by clustered regularly interspaced short palindromic repeat/Cas9 genome-editing technology from a CBA/CaJ background.We observed significant hearing loss and progressive degeneration of stereocilia in the outer hair cells of Tprn-null mice starting from postnatal day 30.Transmission electron microscopy images of stereociliary bundles in the mutant mice showed some stereociliary rootlets with curved shafts.The central cores of the stereociliary rootlets possessed hollow structures with surrounding loose peripheral dense rings.Radixin,a protein expressed at stereocilia tapering,was abnormally dispersed along the stereocilia shafts in Tprn-null mice.The expression levels of radixin andβ-actin significantly decreased.We propose that Tprn is critical to the retention of the integrity of the stereociliary rootlet.Loss of Tprn in Tprn-null mice caused the disruption of the stereociliary rootlet,which resulted in damage to stereociliary bundles and hearing impairments.The generated Tprn-null mice are ideal models of human hereditary deafness DFNB79.

关 键 词：TPRN STEREOCILIA stereociliary rootlet actin filament CRISPR/Cas9 HEARING 

分 类 号：R76[医药卫生—耳鼻咽喉科]