Titre
Role of ectodysplasin signalling in middle ear and nasal pathology in rat and mouse models of hypohidrotic ectodermal dysplasia.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Del-Pozo, J.
Auteure/Auteur
MacIntyre, N.
Auteure/Auteur
Azar, A.
Auteure/Auteur
Headon, D.
Auteure/Auteur
Schneider, P.
Auteure/Auteur
Cheeseman, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1754-8411
Statut éditorial
Publié
Date de publication
2019-04-25
Volume
12
Numéro
4
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
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 <sup>Ta</sup> ) and downless (Edar <sup>dl-J/dl-J</sup> ) 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 <sup>Ta</sup> 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 <sup>swh/swh</sup> than those in unaffected heterozygous Edaradd <sup>swh/+</sup> 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.
Sujets
PID Serval
serval:BIB_4103E7371D49
PMID
Open Access
Oui
Date de création
2019-05-13T06:39:21.129Z
Date de création dans IRIS
2025-05-20T18:51:45Z
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Nom
dmm037804.full.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
5.95 MB
Format
Adobe PDF
PID Serval
serval:BIB_4103E7371D49.P001
URN
urn:nbn:ch:serval-BIB_4103E7371D490
Somme de contrôle
(MD5):207d8568b8cbfdf763fa579f8c1702f8