C3H/HeJ Mouse Model for Spontaneous Chronic Otitis Media

Objectives/Hypothesis: Chronic otitis media is a significant clinical problem. Understanding the mechanisms of chronic otitis media is critical for its control. However, little is known of these processes as a result of lack of animal models of spontaneous otitis media. The C3H/HeJ mouse has a singl...

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Bibliographic Details
Published in:The Laryngoscope 2006-07, Vol.116 (7), p.1071-1079
Main Authors: MacArthur, Carol J., Hefeneider, Steven H., Kempton, J Beth, Trune, Dennis R.
Format: Article
Language:English
Subjects:
Animals
auditory brainstem response
Biological and medical sciences
Chronic Disease
Diagnosis, Differential
Disease Models, Animal
Ear, Inner - pathology
Ear, Middle - pathology
Evoked Potentials, Auditory, Brain Stem - physiology
genetic animal models
inflammation
Medical sciences
Mice
Mice, Inbred C3H
mouse model
Otitis media
Otitis Media - pathology
Otitis Media - physiopathology
Otorhinolaryngology. Stomatology
Otoscopy
Severity of Illness Index
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Summary:Objectives/Hypothesis: Chronic otitis media is a significant clinical problem. Understanding the mechanisms of chronic otitis media is critical for its control. However, little is known of these processes as a result of lack of animal models of spontaneous otitis media. The C3H/HeJ mouse has a single amino acid substitution in its toll‐like receptor 4 (TLR4), making it insensitive to endotoxin. As a result, these mice cannot clear Gram‐negative bacteria. The chronically inflamed middle ear in this animal provides us the opportunity to study spontaneous chronic otitis media. Study Design and Methods: Otoscopy and auditory brain response (ABR) evaluation of C3H/HeJ mice at 3, 5, 7, 9, and 11 months were carried out under sedation. At 12 months of age, mice were killed and histologic analysis of the middle ear, inner ear, and eustachian tube was carried out. Results: Tympanic membrane visualization and ABR thresholds in 7‐ to 8‐month‐old C3H/HeJ mice showed that approximately half developed middle and inner ear disease spontaneously. The significant elevation of thresholds suggested a sensorineural component in addition to the conductive loss. Middle and inner ear histology showed some degree of middle and inner ear inflammation in half the mice, paralleling the ABR data. Conclusions: The histopathologic changes reported here in the C3H/HeJ mouse model of chronic otitis media have been reported in human chronic otitis media. This spontaneous model of chronic otitis media will be valuable for the characterization of middle and inner ear inflammatory disease processes that are induced by middle ear infections.
ISSN:0023-852X
1531-4995
DOI:10.1097/01.mlg.0000224527.41288.c4