Ectodysplasin signalling deficiency in mouse models of hypohidrotic ectodermal dysplasia leads to middle ear and nasal pathology.
Ectodysplasin signalling deficiency in mouse models of hypohidrotic ectodermal dysplasia leads to middle ear and nasal pathology.
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少汗性外胚叶发育不良小鼠模型中的外胚叶发育不良蛋白信号传导缺陷导致中耳和鼻病理学。
DOI：
10.1093/hmg/ddw202
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发表时间：
2016-08-15
影响因子：
3.5
通讯作者：
Cheeseman M
中科院分区：
文献类型：
--
作者：
Azar A;Piccinelli C;Brown H;Headon D;Cheeseman M
少汗性外胚层发育不良（HED）是由EDA、EDAR或EDARADD基因突变引起的，其特征是分泌汗腺、毛囊和牙齿减少或缺失，以及唾液腺、乳腺和颅面腺形成缺陷。患有HED的小鼠模型也携带Eda、Edar或Edaradd突变，并且具有映射到相同结构的缺陷。HED患者有耳鼻喉疾病，但尚未在携带类似基因突变的小鼠中进行研究。我们报道了Eda和Edar突变小鼠中耳炎、鼻炎和鼻咽炎的高频率发生，并探讨了这些系中与腺体功能、微生物和免疫参数相关的致病机制。在HED突变小鼠中，鼻咽听管腺不能发育，其功能影响包括溶菌酶分泌减少、纤毛粘液清除减少和鼻共生菌过度生长并伴有中性粒细胞渗出。重的鼻咽部异物负荷和腺体保护的丧失改变了听筒的门控功能，听筒可发生病理性扩张。大的异物颗粒在大球囊内积聚，刺激肉芽肿的形成。免疫细胞群和骨髓细胞功能分析显示，在HED突变小鼠中没有明显的免疫缺陷的证据。我们使用HED突变小鼠作为人类疾病模型的研究结果支持了这样一种观点，即HED患者的耳鼻部病理是由于鼻和鼻咽腺缺陷、粘膜纤毛清除减少和听管门控功能受损导致的，听管门控功能受损是大球病理后遗症的基础。
Hypohidrotic ectodermal dysplasia (HED) results from mutation of the EDA, EDAR or EDARADD genes and is characterized by reduced or absent eccrine sweat glands, hair follicles and teeth, and defective formation of salivary, mammary and craniofacial glands. Mouse models with HED also carry Eda, Edar or Edaradd mutations and have defects that map to the same structures. Patients with HED have ear, nose and throat disease, but this has not been investigated in mice bearing comparable genetic mutations. We report that otitis media, rhinitis and nasopharyngitis occur at high frequency in Eda and Edar mutant mice and explore the pathogenic mechanisms related to glandular function, microbial and immune parameters in these lines. Nasopharynx auditory tube glands fail to develop in HED mutant mice and the functional implications include loss of lysozyme secretion, reduced mucociliary clearance and overgrowth of nasal commensal bacteria accompanied by neutrophil exudation. Heavy nasopharynx foreign body load and loss of gland protection alters the auditory tube gating function and the auditory tubes can become pathologically dilated. Accumulation of large foreign body particles in the bulla stimulates granuloma formation. Analysis of immune cell populations and myeloid cell function shows no evidence of overt immune deficiency in HED mutant mice. Our findings using HED mutant mice as a model for the human condition support the idea that ear and nose pathology in HED patients arises as a result of nasal and nasopharyngeal gland deficits, reduced mucociliary clearance and impaired auditory tube gating function underlies the pathological sequelae in the bulla.
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影响因子：
4.3
作者：
Hood D;Moxon R;Purnell T;Richter C;Williams D;Azar A;Crompton M;Wells S;Fray M;Brown SD;Cheeseman MT
通讯作者：
Cheeseman MT
影响因子：
2
作者：
Henningsen, Emil;Svendsen, Mathias Tiedemann;Jensen, Peter Kjestrup Axel
通讯作者：
Jensen, Peter Kjestrup Axel
影响因子：
1.8
作者：
Casal, ML;Mauldin, EA;Felsburg, PJ
通讯作者：
Felsburg, PJ
影响因子：
4.5
作者：
Cheeseman MT;Tyrer HE;Williams D;Hough TA;Pathak P;Romero MR;Hilton H;Bali S;Parker A;Vizor L;Purnell T;Vowell K;Wells S;Bhutta MF;Potter PK;Brown SD
通讯作者：
Brown SD
DOI：
10.1016/j.ijporl.2003.09.010
发表时间：
2004-01-01
影响因子：
1.5
作者：
Cayé-Thomasen, P;Tos, M
通讯作者：
Tos, M