机构：[1]Hearing and Speech Rehabilitation Institute, College of Special Education, Binzhou Medical University, Yantai, China[2]Department of Medical Genetics and Cell Biology, Binzhou Medical University, Yantai, China[3]Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China华中科技大学同济医学院附属协和医院[4]Department of Otolaryngology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China深圳市第二人民医院深圳市康宁医院深圳医学信息中心[5]Department of Otolaryngology-Head & Neck Surgery, Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, Xi’an, China[6]Centre for Hearing and Deafness, University at Buffalo, Buffalo, NY, USA[7]Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China首都医科大学附属北京同仁医院研究所眼科研究所[8]Department of Otolaryngology, Case Western Reserve University, Cleveland, OH, USA
Different mutations in the cadherin 23 (CDH23) gene in different genetic backgrounds have been linked to either syndromic or nonsyndromic forms of deafness in humans. We previously reported a progressive hearing loss (HL) mouse model, the Cdh23(erl/erl) mouse, which carries a 208T > C mutation causing an amino acid substitution at S70P in C57BL/6J mice. To investigate the differences in Cdh23 mutation-related HL in different genetic backgrounds, we used the CRISPR/Cas9 system to generate homozygous mice in the CBA/CaJ background that have the same base pair missense mutation (208T > C) (Cdh23(erl2/erl2)) as Cdh23(erl/erl) mice in the C57BL/6J background or a single base pair deletion (235G) (Cdh23(V2J2/V2J2)) in the Cdh23 gene at exon 5. The two mutant mice exhibit hearing impairment across a broad range of frequencies. The progression of HL in Cdh23(erl2/erl2) mice is slower than that in Cdh23(erl/erl) mice. We also found structural abnormalities in the stereocilia of cochlear hair cells in Cdh23(erl2/erl2) and Cdh23(V2J2/V2J2) mice. Cdh23(V2J2/V2J2) mice show signs of vestibular dysfunction in open field behavior and swimming tests. In addition, we observed hair bundle defects in vestibular hair cells in Cdh23(V2J2/V2J2) mice. Our results suggest an interaction between the erl locus and the C57BL/6J background that exacerbates HL in Cdh23(erl/erl) mice. Moreover, our study confirms that the Cdh23 gene is essential for normal hearing and balance. These two novel mutant mouse strains provide excellent models for studying CDH23 mutation-related deafness in humans.
基金：
National Natural Science Foundation
of China (81873697, 81530030, and
81600809); the Shandong Provincial
Natural Science Foundation of China
(ZR2020KH025); the Humanities and
Social Sciences Foundation of the Ministry
of Education of China (18YJC740128);
the China Disabled Persons’ Federation
(CLS2019-02);
the Taishan Scholar
Foundation; the “Clinical Medicine + X”
academic degree program cultivation and
construction project of Binzhou Medical
University; Binzhou Medical University
start-up
fund to RG; the US National
Institutes of Health (R01DC015111 and
R21DC005846).
第一作者机构：[1]Hearing and Speech Rehabilitation Institute, College of Special Education, Binzhou Medical University, Yantai, China
共同第一作者：
通讯作者：
通讯机构：[1]Hearing and Speech Rehabilitation Institute, College of Special Education, Binzhou Medical University, Yantai, China[8]Department of Otolaryngology, Case Western Reserve University, Cleveland, OH, USA[*1]Department of Otolaryngology, Case Western Reserve University, Cleveland, OH 44016, USA.[*2]Hearing and Speech Rehabilitation Institute, College of Special Education, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, China.
推荐引用方式(GB/T 7714)：
Zhao Tong,Ma Peng,Zhao Fangfang,et al.Phenotypic differences in the inner ears of CBA/CaJ and C57BL/6J mice carrying missense and single base pair deletion mutations in the Cdh23 gene[J].JOURNAL OF NEUROSCIENCE RESEARCH.2021,99(10):2743-2758.doi:10.1002/jnr.24905.
APA：
Zhao, Tong,Ma, Peng,Zhao, Fangfang,Zheng, Tihua,Yan, Bin...&Li, Bo.(2021).Phenotypic differences in the inner ears of CBA/CaJ and C57BL/6J mice carrying missense and single base pair deletion mutations in the Cdh23 gene.JOURNAL OF NEUROSCIENCE RESEARCH,99,(10)
MLA：
Zhao, Tong,et al."Phenotypic differences in the inner ears of CBA/CaJ and C57BL/6J mice carrying missense and single base pair deletion mutations in the Cdh23 gene".JOURNAL OF NEUROSCIENCE RESEARCH 99..10(2021):2743-2758
