Open AccessThe EDA-deficient mouse has Zymbal's gland hypoplasia and acute otitis externa
Author(s) -
Jorge del Pozo,
Denis J. Headon,
James D. Glover,
Ali Anvari Azar,
Sonia SchuepbachMallepell,
Mahmood F. Bhutta,
Jon Riddell,
Scott Maxwell,
Elspeth Milne,
Pascal Schneider,
Michael Cheeseman
Publication year - 2022
Publication title -
disease models and mechanisms
Language(s) - English
Resource type - Journals
eISSN - 1754-8411
pISSN - 1754-8403
DOI - 10.1242/dmm.049034
Subject(s) - hypohidrotic ectodermal dysplasia , otitis , ear canal , hypoplasia , biology , endocrinology , medicine , ectodermal dysplasia , genetics , radiology
In mice, rats, dogs and humans, the growth and function of sebaceous glands and eyelid Meibomian glands depend on the ectodysplasin signalling pathway. Mutation of genes encoding the ligand EDA, its transmembrane receptor EDAR and the intracellular signal transducer EDARADD leads to hypohidrotic ectodermal dysplasia, characterised by impaired development of teeth and hair, as well as cutaneous glands. The rodent ear canal has a large auditory sebaceous gland, the Zymbal’s gland, the function of which in the health of the ear canal has not been determined. We report that EDA-deficient mice, EDAR-deficient mice and EDARADD-deficient rats have Zymbal’s gland hypoplasia. EdaTa mice have 25% prevalence of otitis externa at postnatal day 21 and treatment with agonist anti-EDAR antibodies rescues Zymbal’s glands. The aetiopathogenesis of otitis externa involves infection with Gram-positive cocci, and dosing pregnant and lactating EdaTa females and pups with enrofloxacin reduces the prevalence of otitis externa. We infer that the deficit of sebum is the principal factor in predisposition to bacterial infection, and the EdaTa mouse is a potentially useful microbial challenge model for human acute otitis externa.