The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue Model
Nonsyndromic hearing loss (NSHL) is of great clinical importance, and mutations in the <i>GJB2</i> gene and the encoded human CONNEXIN 26 (CX26) protein play important roles in the genetic pathogenesis. The CX26 p.R184Q mutation was shown to be a dominant-negative effect in our previous...
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doaj-4290ff575bba4636992c4cdf207ef3202020-11-25T02:52:01ZengMDPI AGCells2073-44092020-05-0191291129110.3390/cells9051291The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue ModelHsuan-An Su0Ting-Wei Lai1Shuan-Yow Li2Tzu-Rong Su3Jiann-Jou Yang4Ching-Chyuan Su5Department of Medical Education, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 807, TaiwanDepartment of BioMedical Sciences, Chung Shan Medical University, Taichung 402, TaiwanDepartment of BioMedical Sciences, Chung Shan Medical University, Taichung 402, TaiwanAntai Medical Care Corporation Antai Tian-Sheng Memorial Hospital, Pingtung 928, TaiwanDepartment of BioMedical Sciences, Chung Shan Medical University, Taichung 402, TaiwanAntai Medical Care Corporation Antai Tian-Sheng Memorial Hospital, Pingtung 928, TaiwanNonsyndromic hearing loss (NSHL) is of great clinical importance, and mutations in the <i>GJB2</i> gene and the encoded human CONNEXIN 26 (CX26) protein play important roles in the genetic pathogenesis. The CX26 p.R184Q mutation was shown to be a dominant-negative effect in our previous study. Previously, we also demonstrated that zebrafish Cx30.3 is orthologous to human CX26. In the present study, we established transgenic zebrafish models with mutated Cx30.3 specifically expressed in the supporting cells of zebrafish inner ears driven by the <i>agr2</i> promoter, to demonstrate and understand the mechanism by which the human CX26 R.184 mutation causes NSHL. Our results indicated that significant structural changes in the inner ears of transgenic lines with mutations were measured and compared to wild-type zebrafish. Simultaneously, significant alterations of transgenic lines with mutations in swimming behavior were analyzed with the zebrafish behavioral assay. This is the first study to investigate the functional results of the CX26 p.R184Q mutation with in vivo disease models. Our work supports and confirms the pathogenic role of the CX26 p.R184Q mutation in NSHL, with a hypothesized mechanism of altered interaction among amino acids in the connexins.https://www.mdpi.com/2073-4409/9/5/1291non-syndromic hearing losszebrafishGJB2CONNEXIN 26Connexin 30.3behavioral assay |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hsuan-An Su Ting-Wei Lai Shuan-Yow Li Tzu-Rong Su Jiann-Jou Yang Ching-Chyuan Su |
spellingShingle |
Hsuan-An Su Ting-Wei Lai Shuan-Yow Li Tzu-Rong Su Jiann-Jou Yang Ching-Chyuan Su The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue Model Cells non-syndromic hearing loss zebrafish GJB2 CONNEXIN 26 Connexin 30.3 behavioral assay |
author_facet |
Hsuan-An Su Ting-Wei Lai Shuan-Yow Li Tzu-Rong Su Jiann-Jou Yang Ching-Chyuan Su |
author_sort |
Hsuan-An Su |
title |
The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue Model |
title_short |
The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue Model |
title_full |
The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue Model |
title_fullStr |
The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue Model |
title_full_unstemmed |
The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue Model |
title_sort |
functional role of connexin 26 mutation in nonsyndromic hearing loss, demonstrated by zebrafish connexin 30.3 homologue model |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-05-01 |
description |
Nonsyndromic hearing loss (NSHL) is of great clinical importance, and mutations in the <i>GJB2</i> gene and the encoded human CONNEXIN 26 (CX26) protein play important roles in the genetic pathogenesis. The CX26 p.R184Q mutation was shown to be a dominant-negative effect in our previous study. Previously, we also demonstrated that zebrafish Cx30.3 is orthologous to human CX26. In the present study, we established transgenic zebrafish models with mutated Cx30.3 specifically expressed in the supporting cells of zebrafish inner ears driven by the <i>agr2</i> promoter, to demonstrate and understand the mechanism by which the human CX26 R.184 mutation causes NSHL. Our results indicated that significant structural changes in the inner ears of transgenic lines with mutations were measured and compared to wild-type zebrafish. Simultaneously, significant alterations of transgenic lines with mutations in swimming behavior were analyzed with the zebrafish behavioral assay. This is the first study to investigate the functional results of the CX26 p.R184Q mutation with in vivo disease models. Our work supports and confirms the pathogenic role of the CX26 p.R184Q mutation in NSHL, with a hypothesized mechanism of altered interaction among amino acids in the connexins. |
topic |
non-syndromic hearing loss zebrafish GJB2 CONNEXIN 26 Connexin 30.3 behavioral assay |
url |
https://www.mdpi.com/2073-4409/9/5/1291 |
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