Otitis media in a mouse model for Down syndrome

Han, Fengchan; Yu, He; Zhang, Jiangping; Tian, Cong; Schmidt, Cecilia; Nava, Casey; Davisson, Muriel T.; Zheng, Qing Yin

doi:10.1111/j.1365-2613.2009.00677.x

Cited by 27 publications

(28 citation statements)

References 38 publications

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“…Cilia dysfunctions have been implicated in a number of conditions, including neonatal respiratory distress, chronic nasal congestion, bronchiectasis and sinusitis, and chronic otitis media with effusion67810111263646566. Despite the significant association and likely contributory role of cilia in OM671112636667, the most common childhood disease, only a sparse number of studies examined ciliation in the epithelium that lines the middle ear cavity and thus have provided only a partial understanding of ciliation in the middle ear13141617686970. Moreover, the orientation of the cilia, which is the structural feature of cilia critical to their motility output and clearance function, has not even been studied.…”

Section: Discussionmentioning

confidence: 99%

Cilia distribution and polarity in the epithelial lining of the mouse middle ear cavity

Luo

Taylor

et al. 2017

Sci Rep

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The middle ear conducts sound to the cochlea for hearing. Otitis media (OM) is the most common illness in childhood. Moreover, chronic OM with effusion (COME) is the leading cause of conductive hearing loss. Clinically, COME is highly associated with Primary Ciliary Dyskinesia, implicating significant contributions of cilia dysfunction to COME. The understanding of middle ear cilia properties that are critical to OM susceptibility, however, is limited. Here, we confirmed the presence of a ciliated region near the Eustachian tube orifice at the ventral region of the middle ear cavity, consisting mostly of a lumen layer of multi-ciliated and a layer of Keratin-5-positive basal cells. We also found that the motile cilia are polarized coordinately and display a planar cell polarity. Surprisingly, we also found a region of multi-ciliated cells that line the posterior dorsal pole of the middle ear cavity which was previously thought to contain only non-ciliated cells. Our study provided a more complete understanding of cilia distribution and revealed for the first time coordinated polarity of cilia in the epithelium of the mammalian middle ear, thus illustrating novel structural features that are likely critical for middle ear functions and related to OM susceptibility.

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Section: Discussionmentioning

confidence: 99%

Cilia distribution and polarity in the epithelial lining of the mouse middle ear cavity

Luo

Taylor

et al. 2017

Sci Rep

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“…A scoring system of -/+/++/+++ was used to assess the severity of pathology in the middle ears following a previously described method with modifications [22]. Histological analysis of the middle ears of control and mutant mice was performed using an Olympus BX51 microscope.…”

Section: Methodsmentioning

confidence: 99%

Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis

2016

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Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

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“…Thus, it is possible that otitis media and failure of cavitation are related. Several syndromes where there is poor clearance of cells in the middle ear cavity demonstrate this possibility, Down’s Syndrome being a well-known example (104). …”

Section: Other Components Of the Middle Earmentioning

confidence: 99%

Can you hear me now? Understanding vertebrate middle ear development

Chapman¹

2011

Front Biosci

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The middle ear is a composite organ formed from all three germ layers and the neural crest. It provides the link between the outside world and the inner ear, where sound is transduced and routed to the brain for processing. Extensive classical and modern studies have described the complex morphology and origin of the middle ear. Non-mammalian vertebrates have a single ossicle, the columella. Mammals have three functionally equivalent ossicles, designated the malleus, incus and stapes. In this review, I focus on the role of genes known to function in the middle ear. Genetic studies are beginning to unravel the induction and patterning of the multiple middle ear elements including the tympanum, skeletal elements, the air-filled cavity, and the insertion point into the inner ear oval window. Future studies that elucidate the integrated spatio-temporal signaling mechanisms required to pattern the middle ear organ system are needed. The longer-term translational benefits of understanding normal and abnormal ear development will have a direct impact on human health outcomes.

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Otitis media in a mouse model for Down syndrome

Cited by 27 publications

References 38 publications

Cilia distribution and polarity in the epithelial lining of the mouse middle ear cavity

Cilia distribution and polarity in the epithelial lining of the mouse middle ear cavity

Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis

Can you hear me now? Understanding vertebrate middle ear development

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