Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis.
Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis.
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ENPP1ASJ突变小鼠的异位矿化和导电性听力损失，这是一种新的耳炎培养基和鼓膜硬化模型。
DOI：
10.1371/journal.pone.0168159
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Johnson KR
中科院分区：
文献类型：
--
作者：
Tian C;Harris BS;Johnson KR
中耳炎（OM）是中耳的炎症，是儿童和患有许多不同综合征疾病的患者听力损失的常见原因。对人群和小鼠模型的研究表明，OM是一种多因素疾病，有许多环境和遗传因素。在这里，我们报告中耳炎相关的听力损失asj（年龄与关节僵硬）突变小鼠，其中携带点突变的Enpp 1基因。听觉诱发的脑干反应（ABR）测量显示，大约90%的突变小鼠（Enpp 1asj/asj）至少有一只耳朵有中度至重度听力障碍。ABR阈值是可变的，一般随着年龄的增长而升高。通过解剖学和组织学检查，我们发现所有听力受损的Enpp 1asj/asj小鼠均存在渗出性中耳炎（OME）。分泌物的体积和炎性细胞含量在asj突变小鼠中各不相同，但所有突变小鼠的中耳上皮增厚，纤维息肉和分泌粘蛋白的杯状细胞比对照组多。在Enpp 1突变小鼠中观察到的其他异常包括圆窗嵴过度骨化、镫骨动脉增厚和过度钙化、锤骨和砧骨融合以及鼓膜内侧出现白色斑块，其中一些是鼓膜炎的典型症状。在年龄较大的asj突变小鼠的外耳道中检测到过多的黄色分泌物，5个月大时具有100%的听力损失，并且有助于听力损失的进行性。这是第一次报告听力损失和耳朵病理学与Enpp 1突变的小鼠。Enpp 1asj突变小鼠为研究鼓膜炎和渗出性中耳炎提供了一种新的动物模型，也为最近报道的与人类ENPP 1突变相关的听力损失提供了一种特异性模型，该突变导致婴儿全身动脉钙化和低磷酸盐血症性佝偻病。
Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.
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DOI：
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