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Updated: May 7, 2026
Dissection of the Auditory Bulla in Postnatal Mice: Isolation of the Middle Ear Bones and Histological Analysis
Published on: January 4, 2017
Surveying the Down syndrome mouse model resource identifies critical regions responsible for chronic otitis media
Mahmood F Bhutta1, Michael T Cheeseman, Yann Herault
1Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Room 6607 Level 6, Headley Way, Oxford, OX3 9DU, UK, m.bhutta@doctors.org.uk.
Abstract:
Chronic otitis media (OM) is common in Down syndrome (DS), but underlying aetiology is unclear. We analysed the entire available mouse resource of partial trisomy models of DS looking for histological evidence of chronic middle-ear inflammation. We found a highly penetrant OM in the Dp(16)1Yey mouse, which carries a complete trisomy of MMU16. No OM was found in the Dp(17)1Yey mouse or the Dp(10)1Yey mouse, suggesting disease loci are located only on MMU16. The Ts1Cje, Ts1RhR, Ts2Yah, and Ts65Dn trisomies and the transchomosomic Tc1 mouse did not develop OM. On the basis of these findings, we propose a two-locus model for chronic middle-ear inflammation in DS, based upon epistasis of the regions of HSA21 not in trisomy in the Tc1 mouse. We also conclude that environmental factors likely play an important role in disease onset.
Insights
Chronic otitis media (OM) is common in Down syndrome (DS). Researchers found that a specific trisomy on mouse chromosome 16 (MMU16) is linked to OM, suggesting a two-locus model and the role of environmental factors.
Area of Science:
- Genetics
- Otology
- Developmental Biology
Background:
- Chronic otitis media (OM) is a frequent complication in individuals with Down syndrome (DS).
- The precise genetic and molecular underpinnings of OM in DS remain largely undetermined.
- Understanding the etiology of OM in DS is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the genetic basis of chronic middle ear inflammation in mouse models of Down syndrome.
- To identify specific chromosomal regions associated with otitis media susceptibility in DS.
- To propose a genetic model for OM pathogenesis in the context of DS.
Main Methods:
- Histological examination of middle ear tissues from various partial trisomy mouse models of Down syndrome.
- Comparative analysis of OM incidence across different trisomic and trans-chromosomic mouse lines.
- Genetic mapping and analysis of disease loci on mouse chromosome 16 (MMU16).
Main Results:
- A high incidence of chronic otitis media was observed in the Dp(16)1Yey mouse model, carrying a complete trisomy of MMU16.
- No evidence of OM was found in Dp(17)1Yey and Dp(10)1Yey mice, indicating that disease-associated loci are primarily on MMU16.
- Other trisomy models (Ts1Cje, Ts1RhR, Ts2Yah, Ts65Dn) and the Tc1 mouse did not develop OM, supporting a specific chromosomal region involvement.
Conclusions:
- A two-locus model for chronic middle ear inflammation in Down syndrome is proposed, involving epistatic interactions of regions on human chromosome 21 (HSA21).
- The findings strongly implicate specific genetic factors on MMU16 in the development of OM in DS.
- Environmental factors are likely to play a significant role in the onset and progression of otitis media in Down syndrome.
