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

Abstract

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, whose function in the health of the ear canal and tympanic membrane has not been determined. We report that the EDA deficient Tabby (EdaTa) mouse, the EDAR deficient mouse (EdarOVE1B/OVE1B) and the EDARADD deficient sparse and wavy hair rat (Edaraddswh/swh) have Zymbal's gland hypoplasia. EdaTa mice also have ear canal hypotrichosis and a 25% prevalence of otitis externa at P21. Treatment with agonist anti-EDAR antibodies rescues Zymbal's glands and ear canal pilosebaceous units. 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 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, commonly known as swimmer's ear.

The interconnected relationships between middle ear bulla size, cavitation defects, and chronic otitis media revealed in a syndromic mouse model

“…The phenotype was often unilateral, suggesting some stochastic changes or environmental impact. Treatment with enrofloxacin has previously been shown to alleviate otitis externa in mice ( Del-Pozo et al, 2022 ), but had no effect on the incidence of OM in the Eya1 heterozygous mice. Antibiotics delivered to mice in drinking water have been shown to have poor efficacy against bacterial pathogens ( Marx et al, 2014 ).…”

“…Antibiotic treatment from birth was provided by the addition of enrofloxacin (Baytril) to the drinking water at a final concentration of 0.25 g/l. Enrofloxacin is secreted into milk, allowing pups to acquire antibiotics during lactation as well as during drinking water ( Del-Pozo et al, 2022 ). To assess the effect of the environment, mice were rederived via sperm transfer to a clean unit to assess the impact of the environment on the susceptibility to OM.…”

Ear Wax and Its Removal: Current Practices and Recommendations

“…It contains long-chain fatty acids, alcohols, squalene and cholesterol, and is usually unproblematic 6,7. There are species difference in wax production, for example the ratio of sebaceous and ceruminous glands increases from medial to lateral in the dog, and aggregates of glands are found near the tympanic membrane in rodents 8. The reasons for such species differences are not understood.…”

“…In modern times, objects such as cotton buds and hair pins, and trends such as ear-candling have gained popularity for the removal of earwax, although these remain cautioned by medical professionals and literature 8,17,24. There has also been an explosion of cameras and instruments on sale to the public, to enable people to remove their own wax under visualization.…”