Patients with mutations in the ectodysplasin receptor signalling pathway genes - the X-linked ligand ectodysplasin-A (EDA), the receptor EDAR or the receptor adapter EDARADD - have hypohidrotic ectodermal dysplasia (HED). In addition to having impaired development of teeth, hair, eccrine sweat glands, and salivary and mammary glands, HED patients have ear, nose and throat disease. The mouse strains Tabby (Eda^Ta ) and downless (Edar^dl-J/dl-J ) have rhinitis and otitis media due to loss of submucosal glands in the upper airway. We report that prenatal correction of EDAR signalling in Eda^Ta mice with the agonist anti-EDAR antibody rescues the auditory-tube submucosal glands and prevents otitis media, rhinitis and nasopharyngitis. The sparse- and wavy-haired (swh) rat strain carries a mutation in the Edaradd gene and has similar cutaneous HED phenotypes to mouse models. We report that auditory-tube submucosal glands are smaller in the homozygous mutant Edaradd^swh/swh than those in unaffected heterozygous Edaradd^swh/+ rats, and that this predisposes them to otitis media. Furthermore, the pathogenesis of otitis media in the rat HED model differs from that in mice, as otitis media is the primary pathology, and rhinitis is a later-onset phenotype. These findings in rodent HED models imply that hypomorphic as well as null mutations in EDAR signalling pathway genes may predispose to otitis media in humans. In addition, this work suggests that the recent successful prenatal treatment of X-linked HED (XLHED) in humans may also prevent ear, nose and throat disease, and provides diagnostic criteria that distinguish HED-associated otitis media from chronic otitis media with effusion, which is common in children.

中文翻译：

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ectodysplasin信号传导在多汗症下皮外胚层发育不良的大鼠和小鼠模型中的作用。

X连锁配体ectodysplasin-A（EDA），EDAR受体或EDADADD受体接头突变的患者存在外皮发育不良（HED）。除牙齿，头发，内分泌汗腺以及唾液和乳腺的发育受损外，HED患者还患有耳鼻喉疾病。小鼠品系Tabby（Eda ^Ta）和downless（Edar ^{dl-J / dl-J}）由于上呼吸道粘膜下腺的缺失而引起鼻炎和中耳炎。我们报告说Eda ^Ta中EDAR信号的产前校正具有激动剂抗EDAR抗体的小鼠可拯救听觉管粘膜下腺并预防中耳炎，鼻炎和鼻咽炎。稀疏和波浪状（shh）大鼠品系在Edaradd基因中携带一个突变，并且具有与小鼠模型相似的皮肤HED表型。我们报告说，纯合突变体Edaradd swh ^/ swh中的听管粘膜下腺比未受影响的杂合体Edaradd swh ^{/ +中的小}大鼠，这使他们容易患中耳炎。此外，在大鼠HED模型中，中耳炎的发病机制与在小鼠中的不同，因为中耳炎是主要病理，而鼻炎是较晚发作的表型。在啮齿动物HED模型中的这些发现表明，EDAR信号通路基因的亚型突变和无效突变可能易患人类中耳炎。此外，这项工作表明，最近在人身上成功进行X连锁HED（XLHED）的产前治疗也可以预防耳，鼻和喉疾病，并提供了诊断标准，可将HED相关中耳炎与积液与慢性中耳炎区分开来，这在儿童中很常见。