A novel model of spontaneous otitis media with effusion (OME) in the Oxgr1 knock-out mouse
A novel model of spontaneous otitis media with effusion (OME) in the Oxgr1 knock-out mouse
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DOI：
10.1016/j.ijporl.2012.09.037
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发表时间：
2013-01-01
影响因子：
1.5
通讯作者：
North, Paula E.
中科院分区：
文献类型：
--
作者：
Kerschner, Joseph E.;Hong, Wenzhou;North, Paula E.
目的：一种新的小鼠模型，在由Oxgr 1基因编码的G蛋白偶联受体（GPCR）中具有特异性基因突变，导致自发性渗出性中耳炎的易感性。作为一个主要的组成部分，感兴趣的OME，粘蛋白的表达进行了检查，在这个模型中，以评估表达相比，野生型动物和适合作为小鼠模型OME.Method：突变（Oxgr 1（-/-））和野生型（Oxgr 1（+/+））之间的年龄为2和5个月的小鼠进行了检查耳镜检查和听觉脑干反应（ABR）。评价中耳的组织学变化。结果：82%的突变小鼠耳镜检查显示有炎症反应的迹象。在突变小鼠中检测到ABR阈值显著升高，表明听力损失。中耳的组织学分析表明存在炎性细胞、粘膜上皮细胞变化和中耳液。使用细菌18 s rRNA通用引物的RT PCR表明中耳中不存在细菌。敲除小鼠显示Muc 1、Muc 2、Muc 3、Muc 4、Muc 5AC、Muc 5 B、Muc 9、Muc 10、Muc 13、Muc 15、Muc 16、Muc 18、Muc 19和Muc 20的表达。与野生型相比，Muc 5 B和Muc 19在敲除小鼠中耳中的表达有增加的趋势。有没有显着的变化，Muc 2的水平，和Muc 5AC的表达水平低于检测限quantitation.Conclusion：发展的小鼠模型具有遗传缺陷有几个有吸引力的功能。这些动物的OME率高达82%。很明显，这种OME与这些基因敲除小鼠中耳上皮的组织病理学变化有关。尽管在该非激发研究条件下确实存在GFM的β-内酰胺酶失调，但粘液渗出的诱导是明显的。个体动物之间这些差异的根本原因需要进一步研究。鉴于此，Oxgr 1（-/-）模型可能是检查结肠癌中粘蛋白调节的理想模型，并可能开发新的GPCR特异性靶向干预措施来调节这些过程。(c)2012爱思唯尔爱尔兰有限公司保留所有权利。
Objective: A novel mouse model with a specific genetic mutation in a G protein coupled receptor (GPCR) encoded by the Oxgr1 gene results in a predisposition to spontaneous otitis media with effusion. As a primary component of interest in OME, mucin expression was examined in this model to assess expression as compared to wild type animals and suitability as a murine model of OME.Method: Mutant (Oxgr1(-/-)) and wild-type (Oxgr1(+/+)) mice between ages of 2 and 5 months were examined by otoscopy and auditory brainstem response (ABR). Histology changes in the middle ear were evaluated. Expression of mucin genes in the middle ear epithelium was determined using RT-PCR and quantitative PCR.Result: Otoscopic exam showed signs of inflammation in 82% of mutant mice. Significant elevated ABR thresholds were detected in mutant mice indicating hearing loss. Histology analysis of the middle ears demonstrated the presence of inflammatory cells, changes in the mucosal epithelium, and middle ear fluid. RT PCR using universal primers for bacterial 18s rRNA suggested the absence of bacteria in the middle ear. The knockout mice demonstrated expression of Muc1, Muc2, Muc3, Muc4, Muc5AC, Muc5B, Muc9, Muc10, Muc13, Muc15, Muc16, Muc18, Muc19 and Muc20. There was a trend of increase in Muc5B and Muc19 expression in the middle ear of the knockout mice compared to that of wild-type. There was no significant change in the level of Muc2, and Muc5AC was expressed at a level below the detection limit of quantification.Conclusion: Development of a murine model with genetic defect has several attractive features. The rate of OME in these animals is high at 82%. It is clear that this OME is related to histopathologic changes in the middle ear epithelium of these knock-out mice. Induction of mucus effusion is evident though the viation in dysregulation of GFM does exist in this non-challenge study condition. The underlying cause of these differences between individual animal requires further investigation. Given this, the Oxgr1(-/-) model is likely to be an ideal model to examine mucin regulation in MEE and potentially develop novel GPCR-specific targeted interventions to regulate these processes. (c) 2012 Elsevier Ireland Ltd. All rights reserved.