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 Ca(2+) Signaling in Kölliker's Organ.
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 Ca(2+) Signaling in Kölliker's Organ.
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连接蛋白 26 表达降低的小鼠听力获取失败与细胞凋亡相对于自噬的异常阶段以及 Kölliker 器官中 ATP 依赖性 Ca2 信号传导缺陷有关
DOI：
10.3389/fncel.2022.816079
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发表时间：
2022
影响因子：
5.3
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Sun L;Gao D;Chen J;Hou S;Li Y;Huang Y;Mammano F;Chen J;Yang J
编码连接蛋白26(Cx26)的GJB2基因突变是语前遗传性耳聋的主要原因，最常见的突变会导致蛋白质功能的完全丧失。为了研究Cx26缺乏如何导致耳聋，我们检测了出生当天注射他莫昔芬的Gjb2loxP/loxP；ROSA26Creer小鼠的细胞凋亡和自噬水平。断奶后，这些小鼠表现出严重的听力障碍，耳蜗管中Cx26的表达减少。在出生后第1天(P)，在Kölliker器的顶回、中部和基底弯可观察到末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)阳性细胞，伴随着裂解的caspase3表达水平的增加，而自噬相关蛋白Lc3-II、p62和Beclin1的表达水平降低。在Cx26表达降低的Kölliker器官细胞中，我们还发现细胞内ATP水平显著降低，并抑制了细胞外ATP引起的钙反应。这些结果为在Cx26功能丧失所致的非综合征性听力障碍小鼠模型中阻止听力获得的机制提供了新的见解。
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 Gjb2loxP/loxP; ROSA26CreER 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 Ca2+ 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.
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影响因子：
11.4
作者：
Fetoni AR;Zorzi V;Paciello F;Ziraldo G;Peres C;Raspa M;Scavizzi F;Salvatore AM;Crispino G;Tognola G;Gentile G;Spampinato AG;Cuccaro D;Guarnaccia M;Morello G;Van Camp G;Fransen E;Brumat M;Girotto G;Paludetti G;Gasparini P;Cavallaro S;Mammano F
通讯作者：
Mammano F
影响因子：
16.6
作者：
Bowl MR;Simon MM;Ingham NJ;Greenaway S;Santos L;Cater H;Taylor S;Mason J;Kurbatova N;Pearson S;Bower LR;Clary DA;Meziane H;Reilly P;Minowa O;Kelsey L;International Mouse Phenotyping Consortium;Tocchini-Valentini GP;Gao X;Bradley A;Skarnes WC;Moore M;Beaudet AL;Justice MJ;Seavitt J;Dickinson ME;Wurst W;de Angelis MH;Herault Y;Wakana S;Nutter LMJ;Flenniken AM;McKerlie C;Murray SA;Svenson KL;Braun RE;West DB;Lloyd KCK;Adams DJ;White J;Karp N;Flicek P;Smedley D;Meehan TF;Parkinson HE;Teboul LM;Wells S;Steel KP;Mallon AM;Brown SDM
通讯作者：
Brown SDM
影响因子：
5.3
作者：
Guo L;Cao W;Niu Y;He S;Chai R;Yang J
通讯作者：
Yang J
影响因子：
5.5
作者：
Chen, Bei;Xu, Hongen;Tang, Wenxue
通讯作者：
Tang, Wenxue
DOI：
10.1073/pnas.1616061113
发表时间：
2016-11-15
影响因子：
11.1
作者：
Ceriani, Federico;Pozzan, Tullio;Mammano, Fabio
通讯作者：
Mammano, Fabio