Development of a Murine Model for CMV‐Induced Hearing Loss

Abstract

Objective: 1) Illustrate phenotypical evidence of sensorineural hearing loss by showing elevation of auditory evoked brainstem response (ABR) thresholds and diminished distortion product otoacoustic emission (DPOAE) in newborn mice inoculated with murine cytomegalovirus (mCMV). 2) Demonstrate evidence of mCMV-mediated pathology based on microscopic examination of infected cochleas. Method: BALB/c mice were injected at postnatal day 3 with 100 pfu of mCMV; controls received saline. Hearing thresholds were assessed using DPOAE and ABR at 4 weeks of age and onward. Histologic changes in temporal bones were compared between infected and control mice. Results: More than 50% of infected mice had significantly higher DPOAE and ABR thresholds at 4 weeks of age as compared to age-matched controls ( P < .008). Five mice (45%) had profound hearing loss (≥80 dB) at 4 weeks of age; 7 mice (50%) progressed to profound hearing loss at 6 weeks. 40% of mice had asymmetric hearing loss. Temporal bone histology showed diffuse loss of outer hair cells in profoundly deaf mice as compared to controls. Conclusion: Intracerebral injection of mCMV to newborn mice can cause hearing loss with high to low frequency ABR progression, and diminished DPOAE. This hearing loss is asymmetric and progressive, similar to human infection. Histologic examination shows loss of outer hair cells in mCMV infected mice, suggesting that CMV infection may target the outer hair cells. Further studies using this model should shed light on the mechanism underlying CMV-mediated hearing loss and provide foundation for better managing and treatment of the condition.