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Otitis media incidence and impact on the auditory brain stem response in lipopolysaccharide-nonresponsive C3H/HeJ
C R Mitchell1, J B Kempton, B Scott-Tyler
1Oregon Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, Oregon Health Sciences University, Portland 97201-3098, USA.
Abstract:
Although mice of the C3H strain normally respond to bacterial lipopolysaccharide with appropriate immune system activation, mice of the C3H/HeJ substrain do not because of a gene defect. This suggests they may be more susceptible to opportunistic bacterial infections and more likely to have otitis media than a normally responding substrain, such as the C3H/HeSnJ. Therefore these two substrains were evaluated for incidence of spontaneous middle ear disease at 2, 4, 6, 10, 12, 15, and 18 months of age. Auditory brain stem response audiometry to pure tones of 4, 8, 16, 24, and 32 kHz was performed to establish the impact of middle ear disease on auditory function. None of the lipopolysaccharide-responsive C3H/HeSnJ mice demonstrated middle ear disease. However, middle ear disease was present in 33% of the C3H/HeJ mice. The conductive loss caused by the otitis media resulted in auditory brain stem response threshold shifts of 15 to 40 dB SPL, lowered peak amplitudes, and increased latencies. Reduced lipopolysaccharide responsiveness by C3H/HeJ mice makes them less capable of reacting immunologically to bacterial infection and presumably underlies the failure to clear middle ear disease. The C3H/HeJ mouse may provide a valuable model in which to study lipopolysaccharide biologic activity and related middle ear inflammatory or immune mechanisms.
Insights
Mice with a gene defect in lipopolysaccharide (LPS) response, C3H/HeJ, developed middle ear disease (otitis media). This immune deficiency makes them susceptible to infections, unlike normal C3H/HeSnJ mice, highlighting a potential model for studying LPS and ear inflammation.
Area of Science:
- Immunology
- Otolaryngology
- Genetics
Background:
- Mice of the C3H/HeJ substrain possess a gene defect impairing their response to bacterial lipopolysaccharide (LPS).
- This defect may increase susceptibility to opportunistic infections and middle ear disease (otitis media).
Purpose of the Study:
- To evaluate the incidence of spontaneous middle ear disease in C3H/HeJ mice compared to the LPS-responsive C3H/HeSnJ substrain.
- To assess the impact of otitis media on auditory function using auditory brain stem response (ABR) audiometry.
Main Methods:
- Comparative study of C3H/HeJ and C3H/HeSnJ mice at multiple ages (2-18 months).
- Incidence assessment of spontaneous middle ear disease.
- Auditory brain stem response audiometry to pure tones (4-32 kHz) to determine hearing thresholds, peak amplitudes, and latencies.
Main Results:
- No middle ear disease was observed in LPS-responsive C3H/HeSnJ mice.
- Middle ear disease was present in 33% of C3H/HeJ mice.
- Otitis media in C3H/HeJ mice caused significant conductive hearing loss (15-40 dB SPL shifts), reduced ABR peak amplitudes, and increased latencies.
Conclusions:
- Reduced LPS responsiveness in C3H/HeJ mice impairs their immune reaction to bacterial infection, leading to otitis media.
- The C3H/HeJ mouse serves as a valuable model for investigating LPS biologic activity and inflammatory/immune mechanisms in middle ear disease.