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Published on: February 10, 2023
A comparison of different murine models for cytomegalovirus-induced sensorineural hearing loss
Yong Wang1, Rusha Patel, Chongyu Ren
1Division of Otolaryngology-Head and Neck Surgery, University of Utah, Salt Lake City, Utah.
Objectives/Hypothesis:
To compare three different inoculation techniques for the development of cytomegalovirus (CMV)-induced sensorineural hearing loss (SNHL) in a mouse model.
Study Design:
A prospective experimental animal study.
Methods:
BALB/c mice underwent inoculation using green fluorescent protein-expressing mouse cytomegalovirus (mCMV-GFP) via transtympanic (TT), intraperitoneal (IP), or intracranial (IC) routes. Control mice received an equal volume of saline. Hearing thresholds were measured using both distortion product otoacoustic emissions (DPOAE) and evoked auditory brainstem response studies (ABR). Cochleas were harvested for histological examination and cytocochleogram.
Results:
No mice in the TT or IP groups showed significant hearing loss. All infected mice in the IC group showed significantly elevated ABR and DPOAE thresholds at 4 weeks of age. Ten mice (55%) had profound hearing loss (≥80 dB) at 4 weeks of age, while the other eight mice (45%) initially showed moderate hearing loss (≤20 dB), which progressed to profound hearing loss by 6 to 8 weeks. Asymmetric hearing loss was seen in 40% of the mice. Temporal bone histology showed diffuse loss of outer hair cells (OHC). Green fluorescent protein (GFP)-labeled virus was abundant in the spiral ganglion and adjacent to the scala tympani at the basal region of the cochlea at 7 days postinjection, and devoid of GFP labeling by 14 days postinfection.
Conclusions:
Intracerebral injection of mCMV preferentially causes mCMV-mediated hearing loss relative to IP or TT injections. These results are consistent with the hearing loss reported in human congenital infection and may have implications for understanding the pathophysiology of CMV-mediated labyrinthitis.
Insights
Intracranial inoculation of mouse cytomegalovirus (mCMV) in mice caused significant sensorineural hearing loss (SNHL). Other methods like transtympanic or intraperitoneal inoculation did not lead to hearing loss, suggesting IC is a better model for CMV-induced SNHL.
Area of Science:
- Otolaryngology
- Virology
- Genetics
Background:
- Cytomegalovirus (CMV) infection is a leading cause of congenital hearing loss.
- Understanding the mechanisms of CMV-induced hearing loss is crucial for developing effective interventions.
Purpose of the Study:
- To compare the efficacy of three inoculation routes (transtympanic, intraperitoneal, intracranial) for inducing CMV-mediated sensorineural hearing loss (SNHL) in a mouse model.
- To establish a reliable animal model for studying CMV-induced hearing impairment.
Main Methods:
- BALB/c mice were inoculated with mouse cytomegalovirus expressing green fluorescent protein (mCMV-GFP) via transtympanic (TT), intraperitoneal (IP), or intracranial (IC) routes.
- Hearing function was assessed using distortion product otoacoustic emissions (DPOAE) and auditory brainstem response (ABR).
- Cochlear histology and viral distribution were analyzed post-infection.
Main Results:
- Intracranial (IC) inoculation resulted in significant hearing loss, evidenced by elevated ABR and DPOAE thresholds.
- Mice receiving IC inoculation exhibited progressive hearing loss, with 55% developing profound SNHL by 4 weeks.
- Histological analysis revealed outer hair cell loss and viral presence in the cochlear spiral ganglion and scala tympani.
Conclusions:
- Intracerebral mCMV inoculation is an effective method for inducing SNHL in mice, outperforming TT and IP routes.
- This model mimics human congenital CMV infection and provides insights into CMV-induced labyrinthitis.
- The findings support the use of the IC inoculation model for further research into CMV-related hearing pathologies.
