Otitis media in sperm-associated antigen 6 (Spag6)-deficient mice.
Otitis media in sperm-associated antigen 6 (Spag6)-deficient mice.
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精子相关抗原 6 (Spag6) 缺陷小鼠的中耳炎。
DOI：
10.1371/journal.pone.0112879
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Li X;Xu L;Li J;Li B;Bai X;Strauss JF 3rd;Zhang Z;Wang H
哺乳动物SPAG 6蛋白定位于轴丝中央器，并且其是正常鞭毛和纤毛运动所需的。最近的研究表明，该蛋白还调节脑室和气管上皮细胞中的纤毛发生和纤毛极性。活动纤毛也存在于中耳和咽鼓管的上皮细胞中，其中纤毛系统参与中耳中浆液和粘液的运动。纤毛缺陷与中耳炎（OM）相关，推测是由于不能有效地运输流体、粘液和包括微生物的颗粒。我们通过研究Spag 6基因中具有靶向突变的小鼠来研究SPag 6在中耳和咽鼓管中的潜在作用。SPAG 6在中耳上皮细胞的纤毛细胞中表达。纤毛基底足的方向是随机的Spag 6缺陷小鼠中耳上皮细胞，并有相关的平面细胞极性（PCP）蛋白，FZD 6的破坏定位。这些功能与纤毛方向紊乱，扫描电子显微镜证实，这导致不协调的纤毛跳动。Spag 6突变小鼠也易于发生OM。然而，突变型和野生型小鼠之间的细菌种群、上皮杯状细胞密度、粘蛋白表达和咽鼓管角没有显著差异，表明OM是由于继发于纤毛功能障碍的液体和粘液积聚。我们的研究表明Spag 6在小鼠OM发病机制中的作用，可能是通过其在中耳和咽鼓管中的PCP依赖性机制调节纤毛/基体极性中的作用。
Mammalian SPAG6 protein is localized to the axoneme central apparatus, and it is required for normal flagella and cilia motility. Recent studies demonstrated that the protein also regulates ciliogenesis and cilia polarity in the epithelial cells of brain ventricles and trachea. Motile cilia are also present in the epithelial cells of the middle ear and Eustachian tubes, where the ciliary system participates in the movement of serous fluid and mucus in the middle ear. Cilia defects are associated with otitis media (OM), presumably due to an inability to efficiently transport fluid, mucus and particles including microorganisms. We investigated the potential role of SPAG6 in the middle ear and Eustachian tubes by studying mice with a targeted mutation in the Spag6 gene. SPAG6 is expressed in the ciliated cells of middle ear epithelial cells. The orientation of the ciliary basal feet was random in the middle ear epithelial cells of Spag6-deficient mice, and there was an associated disrupted localization of the planar cell polarity (PCP) protein, FZD6. These features are associated with disordered cilia orientation, confirmed by scanning electron microscopy, which leads to uncoordinated cilia beating. The Spag6 mutant mice were also prone to develop OM. However, there were no significant differences in bacterial populations, epithelial goblet cell density, mucin expression and Eustachian tube angle between the mutant and wild-type mice, suggesting that OM was due to accumulation of fluid and mucus secondary to the ciliary dysfunction. Our studies demonstrate a role for Spag6 in the pathogenesis of OM in mice, possibly through its role in the regulation of cilia/basal body polarity through the PCP-dependent mechanisms in the middle ear and Eustachian tubes.
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DOI：
10.1152/ajplung.00444.2006
发表时间：
2007-06-01
影响因子：
4.9
作者：
Rousseau, Karine;Kirkham, Sara;Thornton, David J.
通讯作者：
Thornton, David J.
影响因子：
56.9
作者：
Thompson, Hannah;Tucker, Abigail S.
通讯作者：
Tucker, Abigail S.
影响因子：
5.3
作者：
Wang, YH;Guo, NN;Nathans, J
通讯作者：
Nathans, J
影响因子：
2.9
作者：
Trune DR;Zheng QY
通讯作者：
Zheng QY
影响因子：
--
作者：
Kerschner, Joseph E.;Tripathi, Shivani;Khampang, Pawjai;Papsin, Blake C.
通讯作者：
Papsin, Blake C.