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Failure Of Hearing Acquisition in Mice With Reduced Expression of Connexin 26 Correlates With the Abnormal Phasing of Apoptosis Relative to Autophagy and Defective ATP-Dependent Ca2+ Signaling in Kölliker's Organ.

Authors :
Sun, Lianhua
Gao, Dekun
Chen, Junmin
Hou, Shule
Li, Yue
Huang, Yuyu
Mammano, Fabio
Chen, Jianyong
Yang, Jun
Source :
Frontiers in Cellular Neuroscience; 3/3/2022, Vol. 16, p1-13, 13p
Publication Year :
2022

Abstract

Mutations in the GJB2 gene that encodes connexin 26 (Cx26) are the predominant cause of prelingual hereditary deafness, and the most frequently encountered variants cause complete loss of protein function. To investigate how Cx26 deficiency induces deafness, we examined the levels of apoptosis and autophagy in Gjb2 <superscript>loxP/loxP</superscript>; ROSA26 <superscript>CreER</superscript> mice injected with tamoxifen on the day of birth. After weaning, these mice exhibited severe hearing impairment and reduced Cx26 expression in the cochlear duct. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells were observed in apical, middle, and basal turns of Kölliker's organ at postnatal (P) day 1 (P1), associated with increased expression levels of cleaved caspase 3, but decreased levels of autophagy-related proteins LC3-II, P62, and Beclin1. In Kölliker's organ cells with decreased Cx26 expression, we also found significantly reduced levels of intracellular ATP and hampered Ca<superscript>2+</superscript> responses evoked by extracellular ATP application. These results offer novel insight into the mechanisms that prevent hearing acquisition in mouse models of non-syndromic hearing impairment due to Cx26 loss of function. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16625102
Volume :
16
Database :
Complementary Index
Journal :
Frontiers in Cellular Neuroscience
Publication Type :
Academic Journal
Accession number :
155558823
Full Text :
https://doi.org/10.3389/fncel.2022.816079