C3H/HeJ mouse model for spontaneous chronic otitis media.
OBJECTIVE
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.


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.
MacArthur
Carol J
CJ
Department of Otolaryngology & Oregon Hearing Research Center, Oregon Health & Science University, and the Department of Immunology, Veteran's Affairs Medical Center, Portland, Oregon, USA. macarthc@ohsu.edu
Hefeneider
Steven H
SH
Kempton
J Beth
JB
Trune
Dennis R
DR
D000818:Animals; D002908:Chronic Disease; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000473:pathology; D004432:Ear, Middle / Q000473:pathology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D010033:Otitis Media / Q000473:pathology* / Q000503:physiopathology; D038781:Otoscopy; D012720:Severity of Illness Index