Otoa-flox 基因敲除小鼠

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产品名称

Otoa-flox 基因敲除小鼠

产品编号

S-CKO-08724

品系全称

C57BL/6JCya-Otoaem1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-246190-Otoa-B6J-VA

品系状态

使用本品系发表的文献需注明: Otoa-flox 基因敲除小鼠 mice (Strain S-CKO-08724) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型

基本信息

基因研究概述

质控标准

基因
基因全称
otoancorin
基因别称
-
染色体号
Chr 7 (Mouse)
转录本 ID
NCBI: NM_139310.2 | Ensembl: ENSMUST00000047025
修饰方式
条件性基因敲除
靶向范围
Exon 11
敲除长度
~640 bp
品系说明
该品系是基于策略设计时的数据库信息制作而成,建议您在购买前查询最新的数据库和相关文献,以获取最准确的表型信息。
表型提示
MGI:2149209Mice homozygous for a knock-out allele exhibit hearing loss, detachment of the tectorial membrane from the spiral limbus, abnormal tectorial membrane morphology, absence of Hensen's stripe and increased cochlear nerve coumpond action potential threshold.
Otoa,也称为otoancorin,是一种重要的蛋白质,由OTOA基因编码。OTOA基因位于染色体5q31.1上,编码的蛋白质在耳蜗中高度表达,特别是在内耳毛细胞的底侧膜上。otoancorin被认为在耳蜗发育中起关键作用,特别是在耳蜗的毛细胞和听觉感受器中,它对于维持正常的听觉功能至关重要[1,2,3,4,5,6,7,8]。

OTOA基因的突变已被证实是非综合征型常染色体隐性遗传性耳聋(DFNB22)的主要原因之一。这种耳聋的特点是听力损失通常在出生后不久或儿童早期出现,并且通常是感音神经性听力损失。听力损失的程度可以从轻度到重度不等,并且可能随时间进展[2,3,4,5,6,7,8]。OTOA基因的突变可能导致otoancorin的缺失或功能异常,进而影响耳蜗的正常发育和功能,导致听力损失。

除了突变,OTOA基因还可能发生基因转换,即基因的一部分被伪基因OTOAP1的同源部分所替换。这种基因转换可能导致otoancorin的截断或功能丧失,从而引起听力损失[1]。基因转换的发生可能与非等位基因同源重组有关,这种重组可能发生在OTOA基因和伪基因OTOAP1之间。

除了基因转换,OTOA基因还可能发生拷贝数变异(CNVs),例如缺失或重复。这些CNVs也可能导致otoancorin的缺失或功能异常,从而引起听力损失[4,5,6,7,8]。此外,OTOA基因的突变还可能与其他基因的突变相互作用,导致更复杂的遗传性耳聋表型[9]。

综上所述,OTOA基因的突变和基因转换是非综合征型常染色体隐性遗传性耳聋的重要原因之一。这些突变可能导致otoancorin的缺失或功能异常,进而影响耳蜗的正常发育和功能,导致听力损失。此外,OTOA基因的突变还可能与其他基因的突变相互作用,导致更复杂的遗传性耳聋表型。因此,研究OTOA基因的突变和基因转换对于理解遗传性耳聋的发病机制和开发新的治疗方法具有重要意义。

参考文献:
1. Laurent, Sacha, Gehrig, Corinne, Nouspikel, Thierry, Paoloni-Giacobino, Ariane, Guipponi, Michel. 2021. Molecular characterization of pathogenic OTOA gene conversions in hearing loss patients. In Human mutation, 42, 373-377. doi:10.1002/humu.24167. https://pubmed.ncbi.nlm.nih.gov/33492714/
2. Del Castillo, Ignacio, Morín, Matías, Domínguez-Ruiz, María, Moreno-Pelayo, Miguel A. 2022. Genetic etiology of non-syndromic hearing loss in Europe. In Human genetics, 141, 683-696. doi:10.1007/s00439-021-02425-6. https://pubmed.ncbi.nlm.nih.gov/35044523/
3. Carlson, Ryan J, Walsh, Tom, Mandell, Jessica B, Rubinstein, Jay, King, Mary-Claire. . Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes. In JAMA otolaryngology-- head & neck surgery, 149, 212-222. doi:10.1001/jamaoto.2022.4463. https://pubmed.ncbi.nlm.nih.gov/36633841/
4. Quaio, Caio Robledo D' Angioli Costa, Coelho, Antonio Victor Campos, Moura, Livia Maria Silva, de Almeida, Tatiana Ferreira, de Oliveira Filho, Joao Bosco. 2022. Genomic study of nonsyndromic hearing loss in unaffected individuals: Frequency of pathogenic and likely pathogenic variants in a Brazilian cohort of 2,097 genomes. In Frontiers in genetics, 13, 921324. doi:10.3389/fgene.2022.921324. https://pubmed.ncbi.nlm.nih.gov/36147510/
5. Sommen, Manou, Schrauwen, Isabelle, Vandeweyer, Geert, Huentelman, Matthew J, Van Camp, Guy. 2016. DNA Diagnostics of Hereditary Hearing Loss: A Targeted Resequencing Approach Combined with a Mutation Classification System. In Human mutation, 37, 812-9. doi:10.1002/humu.22999. https://pubmed.ncbi.nlm.nih.gov/27068579/
6. Sugiyama, Kenjiro, Moteki, Hideaki, Kitajiri, Shin-Ichiro, Kosho, Tomoki, Usami, Shin-Ichi. 2019. Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of OTOA-Associated Hearing Loss. In Genes, 10, . doi:10.3390/genes10090715. https://pubmed.ncbi.nlm.nih.gov/31527525/
7. Kim, Bong Jik, Kim, Dong-Kyu, Han, Jin Hee, Park, Sungjin, Choi, Byung Yoon. 2019. Clarification of glycosylphosphatidylinositol anchorage of OTOANCORIN and human OTOA variants associated with deafness. In Human mutation, 40, 525-531. doi:10.1002/humu.23719. https://pubmed.ncbi.nlm.nih.gov/30740825/
8. Yang, J Y, Wang, Q Q, Han, M Y, Dai, P, Yuan, Y Y. . [Phenotype-genotype analysis of the autosomal recessive hereditary hearing loss caused by OTOA variations]. In Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery, 58, 460-469. doi:10.3760/cma.j.cn115330-20220620-00361. https://pubmed.ncbi.nlm.nih.gov/37114731/
9. Failla, Pinella, Saccuzzo, Lucia, Galesi, Ornella, Romano, Corrado, Fichera, Marco. 2024. Unveiling Secondary Mutations in Blended Phenotypes: Dual ERCC4 and OTOA Pathogenic Variants Through WES Analysis. In International journal of molecular sciences, 25, . doi:10.3390/ijms252413471. https://pubmed.ncbi.nlm.nih.gov/39769235/