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.

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