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C3H/HeJ mouse model for spontaneous chronic otitis media
Carol J MacArthur1, Steven H Hefeneider, J Beth Kempton
1Department 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
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.
Insights
The C3H/HeJ mouse spontaneously develops chronic otitis media, offering a new model for studying middle and inner ear inflammation. This research provides insights into inflammatory disease processes following middle ear infections.
Area of Science:
- Otolaryngology
- Immunology
- Animal Models
Background:
- Chronic otitis media (COM) is a prevalent clinical issue with poorly understood mechanisms.
- A lack of spontaneous animal models hinders research into COM pathogenesis.
- The C3H/HeJ mouse, with a mutation in toll-like receptor 4 (TLR4), is endotoxin-insensitive and struggles to clear Gram-negative bacteria.
Purpose of the Study:
- To investigate the C3H/HeJ mouse as a model for spontaneous chronic otitis media.
- To characterize the development of middle and inner ear disease in this model.
- To provide a valuable tool for studying inflammatory processes in COM.
Main Methods:
- Otoscopy and auditory brain response (ABR) evaluations were performed on C3H/HeJ mice at multiple time points (3-11 months).
- Histologic analysis of the middle ear, inner ear, and eustachian tube was conducted at 12 months.
- The study focused on spontaneous disease development in the absence of induced infection.
Main Results:
- Approximately 50% of C3H/HeJ mice spontaneously developed middle and inner ear disease by 7-8 months of age.
- ABR testing revealed significant threshold elevations, indicating both conductive and sensorineural hearing loss.
- Histopathology confirmed inflammation in the middle and inner ears of affected mice, correlating with ABR findings.
Conclusions:
- The C3H/HeJ mouse exhibits spontaneous histopathologic changes consistent with human chronic otitis media.
- This animal model is suitable for studying the inflammatory mechanisms of middle and inner ear diseases.
- The model facilitates research into spontaneous otitis media and its associated inflammatory processes.
