Role of ectodysplasin signalling in middle ear and nasal pathology in rat and mouse models of hypohidrotic ectodermal dysplasia.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_4103E7371D49
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Role of ectodysplasin signalling in middle ear and nasal pathology in rat and mouse models of hypohidrotic ectodermal dysplasia.
Journal
Disease models & mechanisms
Author(s)
Del-Pozo J., MacIntyre N., Azar A., Headon D., Schneider P., Cheeseman M.
ISSN
1754-8411 (Electronic)
ISSN-L
1754-8403
Publication state
Published
Issued date
25/04/2019
Peer-reviewed
Oui
Volume
12
Number
4
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
Animals, Antibodies/pharmacology, Disease Models, Animal, Ear, Middle/metabolism, Ear, Middle/pathology, Ectodermal Dysplasia 1, Anhidrotic/metabolism, Ectodermal Dysplasia 1, Anhidrotic/pathology, Ectodysplasins/metabolism, Female, Hyalin/metabolism, Male, Mice, Nasopharyngitis/complications, Nasopharyngitis/pathology, Nasopharynx/drug effects, Nasopharynx/pathology, Nose/pathology, Otitis Media/complications, Otitis Media/pathology, Phenotype, Rats, Receptors, Ectodysplasin/agonists, Receptors, Ectodysplasin/metabolism, Rhinitis/complications, Signal Transduction, Auditory-tube submucosal gland, EDAR signalling, Eda mouse, Edaradd rat, Otitis media, XLHED
Pubmed
Web of science
Open Access
Yes
Create date
13/05/2019 8:39
Last modification date
24/01/2020 7:19
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