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Abstract / Description of output
Auditory bulla cavitation defects are a cause of otitis media, but the normal cellular pattern of bulla mesenchyme regression and its failure are not well understood. In mice, neural crest derived mesenchyme occupies the bulla from embryonic day 17.5
(E17.5) to postnatal day 11 (P11) and then regresses to form the adult air-filled bulla cavity. We report that bulla mesenchyme is bordered by a single layer of non-ciliated epithelium characterized by interdigitating cells with desmosome cell junctions and a basal lamina, and by Bpifa1 gene expression and laminin staining of the basal lamina. At P11-P12 the mesenchyme shrinks; mesenchyme-associated epithelium shortens and mesenchymal cells and extracellular matrix collagen fibrils condense culminating in the formation of cochlea promontory mucosa bordered by compact non-ciliated epithelial cells. FBXO11 is a candidate disease gene in human chronic otitis media with effusion and we report that a bulla cavitation defect initiates the pathogenesis of otitis media in the established mouse model Jeff (Fbxo11Jf/+). Persistent mesenchyme in Fbxo11Jf/+ bullae has limited mesenchymal cell condensation, fibrosis and hyperplasia of the mesenchyme-associated epithelium. Subsequent modification forms fibrous adhesions that link the mucosa and the tympanic membrane and this is accompanied dystrophic mineralization and accumulation of serous effusion in the bulla cavity. Mouse models of bulla cavitation defects are important because their study in humans is limited to post mortem samples. This work indicates new diagnostic criteria for this otitis media aetiology in
humans, and the prospects of studying the molecular mechanisms of murine bulla cavitation in organ culture.
(E17.5) to postnatal day 11 (P11) and then regresses to form the adult air-filled bulla cavity. We report that bulla mesenchyme is bordered by a single layer of non-ciliated epithelium characterized by interdigitating cells with desmosome cell junctions and a basal lamina, and by Bpifa1 gene expression and laminin staining of the basal lamina. At P11-P12 the mesenchyme shrinks; mesenchyme-associated epithelium shortens and mesenchymal cells and extracellular matrix collagen fibrils condense culminating in the formation of cochlea promontory mucosa bordered by compact non-ciliated epithelial cells. FBXO11 is a candidate disease gene in human chronic otitis media with effusion and we report that a bulla cavitation defect initiates the pathogenesis of otitis media in the established mouse model Jeff (Fbxo11Jf/+). Persistent mesenchyme in Fbxo11Jf/+ bullae has limited mesenchymal cell condensation, fibrosis and hyperplasia of the mesenchyme-associated epithelium. Subsequent modification forms fibrous adhesions that link the mucosa and the tympanic membrane and this is accompanied dystrophic mineralization and accumulation of serous effusion in the bulla cavity. Mouse models of bulla cavitation defects are important because their study in humans is limited to post mortem samples. This work indicates new diagnostic criteria for this otitis media aetiology in
humans, and the prospects of studying the molecular mechanisms of murine bulla cavitation in organ culture.
Original language | English |
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Article number | dmm038315 |
Pages (from-to) | 1-10 |
Journal | Disease Models and Mechanisms |
Volume | 12 |
DOIs | |
Publication status | Published - 21 Mar 2019 |
Keywords / Materials (for Non-textual outputs)
- BPIFA1
- Neural-crest-derived epithelium
- Keratins 5, 8, 7 and 19
- BCL6
- SNAI1
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Dive into the research topics of 'Chronic otitis media is initiated by a bulla cavitation defect in the FBXO11 mouse model'. Together they form a unique fingerprint.Projects
- 2 Finished
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R43494 Advancing our capabilities for visualization of cellular structures and isolated complexes byelectron microscopy
Böttcher, B. & Schirmer, E.
22/06/15 → 21/06/20
Project: Research
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Control of development and reproductive traits
Burdon, T., Argyle, D., Ashworth, C., Beard, P., Brunton, P., Burt, D., Clinton, M., Dunn, I., Farquharson, C., Headon, D., Hocking, P., Hohenstein, P., Hume, D., Jackson, I., McColl, B., McGrew, M., McLachlan, G., Sang, H., Summers, K. & Whitelaw, B.
1/04/12 → 31/03/17
Project: Research
Profiles
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Jorge Del-Pozo
- Royal (Dick) School of Veterinary Studies - Personal Chair of Veterinary Anatomic Pathology
Person: Academic: Research Active