PMID- 31034913
OWN - NLM
STAT- MEDLINE
DCOM- 20200424
LR  - 20211204
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 128
DP  - 2019 Sep
TI  - Reduced postnatal expression of cochlear Connexin26 induces hearing loss and 
      affects the developmental status of pillar cells in a dose-dependent manner.
PG  - 196-205
LID - S0197-0186(19)30157-3 [pii]
LID - 10.1016/j.neuint.2019.04.012 [doi]
AB  - Mutations in the GJB2 gene (which encodes Connexin26 (Cx26)) are the most common 
      cause of non-syndromic deafness. Previous studies showed that an extensive 
      knockout of the Gjb2 gene in cochlear epithelium can cause severe deafness, 
      significant hair cell (HC) loss and failure of pillar cells (a type of supporting 
      cell, PCs) to differentiate in mice. This study aimed to establish different 
      mouse models with gradient reductions of cochlear Cx26 expression and to 
      investigate the effect of different reduced levels of cochlear Cx26 expression on 
      hearing and development of PCs. According to the reduction in the levels of 
      cochlear Cx26, these models were named high knockdown (KD), middle KD and low KD 
      group. In the low KD group, the mice showed normal hearing and well-developed 
      PCs. In the high KD group, up to 90 percent of supporting cells (SCs) lost Cx26 
      expression. These mice exhibited severe deafness, rapid hair cell degeneration 
      and juvenile PCs. In the middle KD group, nearly half of SCs lost Cx26 
      expression. However, these mice showed a moderate deafness and a late-onset hair 
      cell loss. Moreover, nearly all the PCs in mice of this group were in a partially 
      differentiated state. These results indicated that reduction of postnatal 
      expression of cochlear Cx26 induces hearing loss in a dose-dependent manner. Null 
      Cx26 in a few SCs affects the developmental status of PCs and the hair cell 
      degeneration pattern. The abnormal developmental status of PCs may be a potential 
      cause of Gjb2-related hearing loss.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Xie, Le
AU  - Xie L
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, 430022, China.
FAU - Chen, Sen
AU  - Chen S
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, 430022, China.
FAU - Xu, Kai
AU  - Xu K
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, 430022, China.
FAU - Cao, Hai-Yan
AU  - Cao HY
AD  - Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Du, An-Na
AU  - Du AN
AD  - Centre of Instrumental Analysis and Metrology, Wuhan Institute of Virology, 
      Chinese Academy of Sciences, Wuhan, 430071, China.
FAU - Bai, Xue
AU  - Bai X
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, 430022, China.
FAU - Sun, Yu
AU  - Sun Y
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic 
      address: sunyu@hust.edu.cn.
FAU - Kong, Wei-Jia
AU  - Kong WJ
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, 430022, China; Institute of 
      Otorhinolaryngology, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, 430022, China. Electronic address: entwjkong@hust.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190426
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Connexins)
RN  - 0 (Gjb2 protein, mouse)
RN  - 127120-53-0 (Connexin 26)
SB  - IM
MH  - Animals
MH  - Cochlea/*metabolism/pathology/*ultrastructure
MH  - Connexin 26
MH  - Connexins/*biosynthesis/genetics
MH  - *Gene Expression Regulation, Developmental
MH  - Hearing Loss/*metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
OTO - NOTNLM
OT  - Connexin26
OT  - Development
OT  - GJB2
OT  - Hearing loss
OT  - Supporting cell
OT  - pillar cell
EDAT- 2019/04/30 06:00
MHDA- 2020/04/25 06:00
CRDT- 2019/04/30 06:00
PHST- 2019/03/18 00:00 [received]
PHST- 2019/04/17 00:00 [revised]
PHST- 2019/04/19 00:00 [accepted]
PHST- 2019/04/30 06:00 [pubmed]
PHST- 2020/04/25 06:00 [medline]
PHST- 2019/04/30 06:00 [entrez]
AID - S0197-0186(19)30157-3 [pii]
AID - 10.1016/j.neuint.2019.04.012 [doi]
PST - ppublish
SO  - Neurochem Int. 2019 Sep;128:196-205. doi: 10.1016/j.neuint.2019.04.012. Epub 2019 
      Apr 26.