Linear acceleration response variation in inbred strains of mice: the requisite for gene discovery

Objectives: (1) Evaluate gravity receptor function using vestibular evoked potentials (VsEPs) recordings in different strains of mice. (2) Indicate functional variation in VsEPs response parameters across strains for the Genome‐Wide Association Study (GWAS) mapping of the vestibular system. Methods: Mice (6 weeks old) were anesthetized with ketamine 100 mg/kg and xylazine 10 mg/kg and were positioned supine with the head mount coupled and the cranium securely fastened to a mechanical shaker. Stimuli consisted of linear acceleration (17 pulses/s) applied to the cranium in the naso‐occipital axis. The first (P1) and second (P2) positive and negative response peaks were measured as phenotypes. Mice were selected based on a combined set of classic inbred (CI) and recombinant inbred (RI) strains from the Hybrid Mouse Diversity Panel (HMDP). A total of 13 CI (C57BL/6J, FVB/NJ, Balb/cJ, C3H/HeJ, Balb/cByJ, AKR/J, 129x1/SvJ, A/J, DBA/2J, SJL/J, CBA/J, SEA/GnJ, and NOD/ShiLtJ) and 10 RI (BXA14/PgnJ, BXD84/RwwJ, BXH19/TyJ, BXH22/KccJ, BXH9/TyJ, BXH10/TyJ, BXA14/PgnJ, BXA4/PgnJ, BXA16/PgnJ, and CXB9/HiAJ) were evaluated with an average of 2.7 mice/strain. Results: A wide range of phenotypic responses was observed. The mean threshold (–8.73 ± 5.1 dB re: 1 g/ms) and P2‐N2 amplitude at +6 dB re: 1 g/ms (0.682 ± 0.51 mV) both demonstrated statistical significant variation (analysis of variance) in VsEP thresholds ( P =. 008) and P2‐N2 amplitude ( P =. 001). Conclusions: These data demonstrate significant variation in VsEP response parameters across strains, strongly suggesting the hypothesis that there exists functional variation of vestibular function among strains of mice and the genetic determinants of such variation can be mapped using GWAS.