The EDA-deficient mouse has Zymbal's gland hypoplasia and acute otitis externa.

Jorge Del-Pozo,Elspeth Milne,Jon Riddell,Scott Maxwell,Pascal Schneider,Michael Cheeseman,Sonia Schuepbach-Mallepell,Mahmood F Bhutta,Denis J Headon,Ali Azar,James D Glover

doi:10.1242/dmm.049034

Jorge Del-Pozo, Elspeth Milne + Show 9 more

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https://doi.org/10.1242/dmm.049034

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Abstract

ABSTRACTIn 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.

Highlights

Human acute otitis externa (AOE) is a common microbial infection of the ear canal with an estimated 1.72 million cases in the US in 2014 at an estimated annual treatment cost of $564 million (Collier et al, 2021)
Hair follicles are reduced in number in EDA deficient Tabby (EdaTa) ear canal skin (Grüneberg, 1971) but we were careful to exclude any sebaceous glands associated with a hair follicle
In Postnatal day 10 (P10) (Fig. 5 A-F) and P30 (Fig. 5 G-I) FVB mice we found the greatest density of punctate Edar ISH signals in basal cells of at the periphery of the Zymbal’s gland lobules (Fig. 5 F,I) whereas the positive control probe, detecting ubiquitin C (Ubc), showed signals were abundant in all gland cell types (Fig. 5 D)

Summary

Introduction

Human acute otitis externa (AOE) is a common microbial infection of the ear canal (external acoustic meatus) with an estimated 1.72 million cases in the US in 2014 at an estimated annual treatment cost of $564 million (Collier et al, 2021). Wetting of the ear canal through swimming, bathing or high environmental humidity compromises these defences and predisposes to microbial infection giving rise to its common name ‘swimmer’s ear’. Animal models of AOE generally involve disrupting the ear canal epithelial barrier by mechanical abrasion, sustained wetting or chemical irritants and inoculation of a microbial pathogen. Spontaneous otitis externa is not a notable disease of laboratory rats, guinea pigs or mice in lab animal medicine texts (Fox et al, 2015)

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