Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, China.
PLoS One. 2011;6(7):e22622. doi: 10.1371/journal.pone.0022622. Epub 2011 Jul 27.
Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2b(nee) mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2b(nee) mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) mirrors craniofacial dysmorphology and otitis media in humans.
发育过程中基因突变引起的颅面缺陷会增加咽鼓管功能障碍的易感性。这些缺陷可导致中耳炎发病率增加。我们研究了 Sh3pxd2b 基因突变（Sh3pxd2b(nee)）对各种发育阶段中耳炎和听力损伤进展的影响。我们发现，所有携带 Sh3pxd2b(nee)突变的小鼠都出现了颅面畸形，并在 11 天大时就出现了中耳炎。我们通过扫描电子显微镜发现，Sh3pxd2b(nee)突变小鼠中耳黏膜的纤毛和杯状细胞有明显变化。通过测量颅面尺寸，我们首次在动物模型中确定，与咽鼓管位置更水平一致，这种小鼠的咽鼓管形态发生了改变。所有突变体均存在听力损伤。免疫组织化学和半定量 RT-PCR 分析发现，突变小鼠耳部 TNF-α 和 TLR2 的表达上调，这与中耳炎的炎症有关。Sh3pxd2b 基因突变（Sh3pxd2b(nee)）的小鼠模型模拟了人类的颅面畸形和中耳炎。
