An in vitro mouse model of congenital cytomegalovirus-induced pathogenesis of the inner ear cochlea.
An in vitro mouse model of congenital cytomegalovirus-induced pathogenesis of the inner ear cochlea.
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DOI：
10.1002/bdra.23105
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发表时间：
2013-02
影响因子：
--
通讯作者：
Jaskoll, Tina
中科院分区：
文献类型：
--
作者：
Melnick, Michael;Jaskoll, Tina
关键词：
先天性人巨细胞病毒（CMV）感染是出生时感音神经性听力损失（SNHL）和出生时未表达的舌前感音神经性听力损失的主要非遗传病因。先天性巨细胞病毒感染婴儿的颞骨尸检标本的缺乏阻碍了组织病理学与发病机制的关键相关性。在这里，我们提出了一个体外胚胎小鼠模型CMV感染的耳蜗，模仿人类网站的病毒感染和相关的病理。CMV感染的小鼠耳蜗上皮细胞和间充质细胞，包括柯替氏器、支持细胞和血管纹均发生明显的异常增生。这与p19、p21、p27和Pcna基因表达以及增殖细胞核抗原（PCNA）蛋白表达的显著失调同时发生。与已知的耳聋基因突变引起的那些类似的其他病理包括血管纹中KCNQ1蛋白表达的下调，以及黑素细胞发育不良和畸形。因此，该模型提供了一个相关且可靠的平台，可以在其中研究巨细胞病毒诱导的耳聋的详细细胞和分子生物学。
Congenital human cytomegalovirus (CMV) infection is the leading nongenetic etiology of sensorineural hearing loss (SNHL) at birth and prelingual SNHL not expressed at birth. The paucity of temporal bone autopsy specimens from infants with congenital CMV infection has hindered the critical correlation of histopathology with pathogenesis. Here, we present an in vitro embryonic mouse model of CMV-infected cochleas that mimics the human sites of viral infection and associated pathology. There is a striking dysplasia/hyperplasia in mouse CMV-infected cochlear epithelium and mesenchyme, including organ of Corti hair and supporting cells and stria vascularis. This is concomitant with significant dysregulation of p19, p21, p27, and Pcna gene expression, as well as proliferating cell nuclear antigen (PCNA) protein expression. Other pathologies similar to those arising from known deafness gene mutations include downregulation of KCNQ1 protein expression in the stria vascularis, as well as hypoplastic and dysmorphic melanocytes. Thus, this model provides a relevant and reliable platform within which the detailed cell and molecular biology of CMV-induced deafness may be studied.
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影响因子：
6.7
作者：
Hertel L;Chou S;Mocarski ES
通讯作者：
Mocarski ES
DOI：
10.1083/jcb.137.6.1287
发表时间：
1997-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hasson T;Gillespie PG;Garcia JA;MacDonald RB;Zhao Y;Yee AG;Mooseker MS;Corey DP
通讯作者：
Corey DP
影响因子：
6.4
作者：
BASKAR, JF;STANAT, SC;HUANG, ES
通讯作者：
HUANG, ES
影响因子：
2.8
作者：
CABLE, J;BARKWAY, C;STEEL, KP
通讯作者：
STEEL, KP
DOI：
10.1073/pnas.92.21.9815
发表时间：
1995-10-10
影响因子：
11.1
作者：
HASSON, T;HEINTZELMAN, MB;MOOSEKER, MS
通讯作者：
MOOSEKER, MS