An Integrated System for Comprehensive Mouse Peripheral Vestibular Function Evaluation Based on Vestibulo-ocular...

In the fields of both vestibular and auditory research, reliable vestibular function tests are essential. However, unlike the auditory function tests, which use standard Auditory Brainstem Response (ABR) equipment, there is no equivalent widely adopted apparatus for vestibular tests. Vestibulo-ocular reflexes (VORs) are the compensatory ocular reflexes that ensure stable vision during head motion. VORs are widely used in clinics to diagnose vestibular deficits. In the research, VORs have been used by various groups to evaluate the mouse vestibular function. However, the effectiveness of VOR tests has not been systematically evaluated with appropriate mouse models, and the lack of commercial equipment hampers its accessibility, confining vestibular testing to a select few labs.

In this study, we developed an integrated and surgery-free instrument system with both angular VOR (aVOR) and off-vertical axis rotation (OVAR) modes for evaluating mouse vestibular function. In addition, the eye rotation calibrations used in this study standardize the data between instruments. To demonstrate its validity and efficacy of the testing equipment, we evaluated four mouse models, including both genders, with peripheral vestibular deficits: 1) mice injected with the vestibulotoxic drug 3,3'-iminodiproprionitrile (IDPN, 2 mg/g and 4 mg/g, 3 male/3 female per group); 2) Critical MET-related mutant mice (Cdh23^v2J/v2J, 4 male/4 female and TMC1^-/-, 6 male/5 female); 3) Vestibular-specific mutant mice (Zpld1^-/-, 6 male/6 female, for semicircular canal dysfunction and Otop1^tlt/tlt, 3 male/2 female, for otoconia deficient); 4) Unilateral vestibular lesion (UVL) mouse model (3 male/3 female per group) where gentamicin was injected into horizontal semicircular canal.

The results showed: 1) Quantification of vestibular deficits can be achieved as a daily routine; 2) Both the horizontal semicircular canal and otolith organs can be assessed, respectively; and 3) The lesion side of UVL can be identified.

These test results reveal the potential of our system as standard equipment for evaluating common vestibular deficits in mice.