690. A Murine Model of Cytomegalovirus Associated Vestibular Function Abnormalities and Hearing Loss
Session: Abstracts: Virology
Friday, October 22, 2010
Background: The most common infectious cause of hearing loss in the developed world, congenital cytomegalovirus (CMV) infection has only recently been described to cause vestibular system abnormalities as well.  We have developed a mouse model system of murine CMV (MCMV) infection in the developing brain to investigate the molecular pathways involved in the development of CMV-associated disease.

Methods: Newborn BALB/c mice were infected with a non-lethal intraperitoneal inoculum of MCMV.  At 6-8 weeks of age, mice were tested by 2 methods for sensorimotor coordination. (1) Balance Beam: 19 infected mice and 19 controls were trained on a 90 cm long, 1.6 cm diameter round balance beam.  The following day, each animal was given one trial and foot slips were counted.  (2) Rotarod: 25 infected mice and 25 controls were evaluated by rotarod treadmill testing [steady accelerating program, 4 rpm to 40 rpm over 4 minutes, measure is time latency to failure (fall or cling), first trial].  At 12-16 weeks old, these same animals were evaluated for sensorineural hearing function using auditory brainstem evoked-response (ABR: 4, 8, 16, 32 kHz and click stimuli) and distortion product otoacoustic emissions (DPOAE).

Results: MCMV infected mice demonstrated twice the number of foot slips across a balance beam when compared to uninfected control animals (4.5 faults over 90 cm vs. 2.3 faults, p = 0.02, Mann-Whitney).  On the accelerating rotarod treadmill, infected animals failed at a mean of 64 seconds, compared to 88 seconds for age-matched uninfected controls (p = 0.005, Mann-Whitney).  ABRs demonstrated a significant difference in hearing acuity at every stimulus (4 kHz: 90.8 dB vs. 66.4 dB, 8 kHz: 57.2 dB vs. 36 dB, 16 kHz: 49.8 dB vs. 35.6 dB, 32 kHz: 68.8 dB vs. 55 dB, Click: 57.6 dB vs. 42.1 dB, all p <  0.0001).  When evaluated by DPOAE, a significant change in mean SPL threshold was seen only at 8 kHz (14 dB, p = 0.0002). 

Conclusion: We demonstrate a small-animal model system in which mice infected with MCMV at birth develop sensorimotor coordination abnormalities and hearing loss when compared to age-matched control animals.  Further study of the pathogenesis of these deficits in these animals promises to shed light on similar mechanisms in children with congenital CMV infection.

Subject Category: P. Pediatric and perinatal infections

Russell D. Bradford, MD, MSPH , University of Alabama at Birmingham, Birmingham, AL
Glenn Bantug, PhD , University of Alabama at Birmingham, Birmingham, AL
William J. Britt, M.D. , Pediatric Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL


R. D. Bradford, None

G. Bantug, None

W. J. Britt, None

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