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F-Actin Dysplasia Involved in Organ of Corti Deformity in Gjb2 Knockdown Mouse Model

Mutations in the GJB2 gene encoding connexin26 (Cx26) protein are one of the most common causes of hereditary deafness. Previous studies have found that different Cx26-null mouse models have severe hearing loss and deformity of the organ of Corti (OC) as well as a reduction in microtubules in pillar...

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Autores principales: Liu, Xiao-zhou, Jin, Yuan, Chen, Sen, Xu, Kai, Xie, Le, Qiu, Yue, Wang, Xiao-hui, Sun, Yu, Kong, Wei-jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957075/
https://www.ncbi.nlm.nih.gov/pubmed/35345836
http://dx.doi.org/10.3389/fnmol.2021.808553
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author Liu, Xiao-zhou
Jin, Yuan
Chen, Sen
Xu, Kai
Xie, Le
Qiu, Yue
Wang, Xiao-hui
Sun, Yu
Kong, Wei-jia
author_facet Liu, Xiao-zhou
Jin, Yuan
Chen, Sen
Xu, Kai
Xie, Le
Qiu, Yue
Wang, Xiao-hui
Sun, Yu
Kong, Wei-jia
author_sort Liu, Xiao-zhou
collection PubMed
description Mutations in the GJB2 gene encoding connexin26 (Cx26) protein are one of the most common causes of hereditary deafness. Previous studies have found that different Cx26-null mouse models have severe hearing loss and deformity of the organ of Corti (OC) as well as a reduction in microtubules in pillar cells (PCs). To explore the underlying mechanism of OC deformity caused by Cx26 downregulation further, we established Cx26 knockdown (KD) mouse models at postnatal days (P)0 and P8. The actin filaments contained in the pillar cells of mice in the P0 KD group were reduced by 54.85% and vinculin was increased by 22%, while the outer hair cells (OHCs) showed normal F-actin content. In the P8 KD group, PCs and OHCs of mice also showed almost normal F-actin content. The G-actin/F-actin ratio increased by 38% in the P0 KD group. No significant change was found in the mRNA or protein expression level of G-actin or the cadherin–catenin core complex in the P0 KD group at P6. Moreover, immunofluorescence showed that the intensity of LRRK2 was reduced by 97% in the P0 KD group at P6. Our results indicate that Cx26 is involved in the maturation of the cytoskeleton during the development of the OC at the early postnatal stage. The polymerization of G-actin into F-actin is prevented in Cx26 KD mice.
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spelling pubmed-89570752022-03-27 F-Actin Dysplasia Involved in Organ of Corti Deformity in Gjb2 Knockdown Mouse Model Liu, Xiao-zhou Jin, Yuan Chen, Sen Xu, Kai Xie, Le Qiu, Yue Wang, Xiao-hui Sun, Yu Kong, Wei-jia Front Mol Neurosci Molecular Neuroscience Mutations in the GJB2 gene encoding connexin26 (Cx26) protein are one of the most common causes of hereditary deafness. Previous studies have found that different Cx26-null mouse models have severe hearing loss and deformity of the organ of Corti (OC) as well as a reduction in microtubules in pillar cells (PCs). To explore the underlying mechanism of OC deformity caused by Cx26 downregulation further, we established Cx26 knockdown (KD) mouse models at postnatal days (P)0 and P8. The actin filaments contained in the pillar cells of mice in the P0 KD group were reduced by 54.85% and vinculin was increased by 22%, while the outer hair cells (OHCs) showed normal F-actin content. In the P8 KD group, PCs and OHCs of mice also showed almost normal F-actin content. The G-actin/F-actin ratio increased by 38% in the P0 KD group. No significant change was found in the mRNA or protein expression level of G-actin or the cadherin–catenin core complex in the P0 KD group at P6. Moreover, immunofluorescence showed that the intensity of LRRK2 was reduced by 97% in the P0 KD group at P6. Our results indicate that Cx26 is involved in the maturation of the cytoskeleton during the development of the OC at the early postnatal stage. The polymerization of G-actin into F-actin is prevented in Cx26 KD mice. Frontiers Media S.A. 2022-03-07 /pmc/articles/PMC8957075/ /pubmed/35345836 http://dx.doi.org/10.3389/fnmol.2021.808553 Text en Copyright © 2022 Liu, Jin, Chen, Xu, Xie, Qiu, Wang, Sun and Kong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Liu, Xiao-zhou
Jin, Yuan
Chen, Sen
Xu, Kai
Xie, Le
Qiu, Yue
Wang, Xiao-hui
Sun, Yu
Kong, Wei-jia
F-Actin Dysplasia Involved in Organ of Corti Deformity in Gjb2 Knockdown Mouse Model
title F-Actin Dysplasia Involved in Organ of Corti Deformity in Gjb2 Knockdown Mouse Model
title_full F-Actin Dysplasia Involved in Organ of Corti Deformity in Gjb2 Knockdown Mouse Model
title_fullStr F-Actin Dysplasia Involved in Organ of Corti Deformity in Gjb2 Knockdown Mouse Model
title_full_unstemmed F-Actin Dysplasia Involved in Organ of Corti Deformity in Gjb2 Knockdown Mouse Model
title_short F-Actin Dysplasia Involved in Organ of Corti Deformity in Gjb2 Knockdown Mouse Model
title_sort f-actin dysplasia involved in organ of corti deformity in gjb2 knockdown mouse model
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957075/
https://www.ncbi.nlm.nih.gov/pubmed/35345836
http://dx.doi.org/10.3389/fnmol.2021.808553
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