Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses

Abstract

The common occurrence of hearing loss in both humans and mice, and the anatomical and functional similarities of their inner ears, attest to the potential of mice being used as models to study inherited hearing loss. A large-scale, auditory screening project is being undertaken at The Jackson Laboratory (TJL) to identify mice with inherited hearing disorders. To assess hearing sensitivity, at least five mice from each inbred strain had auditory brainstem response (ABR) thresholds determined. Thus far, we have screened 80 inbred strains of mice; 60 of them exhibited homogeneous ABR threshold values not significantly different from those of the control strain CBA/CaJ. This large database establishes a reliable reference for normal hearing mouse strains. The following 16 inbred strains exhibited significantly elevated ABR thresholds before the age of 3 months: 129/J, 129/ReJ, 129/SvJ, A/J, ALR/LtJ, ALS/LtJ, BUB/BnJ, C57BLKS/J, C57BR/cdJ, C57L/J, DBA/2J, I/LnJ, MA/MyJ, NOD/LtJ, NOR/LtJ, and SKH2/J. These hearing impaired strains may serve as models for some forms of human non-syndromic hearing loss and aid in the identification of the underlying genes.

Fig. 1

Determination of ABR thresholds. Normal ABR patterns for a 32 week old CBA/CaJ mouse (A) induced by click stimuli of 65, 55, 45, 35 and 30 dB SPL. The ABR threshold for this mouse was estimated to be 35 dB SPL. (There are usually 4 or 5 response peaks, labeled I, II, II, and IV respectively.) ABR patterns for a 5 week old DBA/2J mouse (B) induced by click stimuli of 90, 80, 70, 65 and 60dB SPL. The ABR threshold for this mouse was estimated to be 65 dB SPL. Response amplitudes for all four stimuli are shown on the same fixed scale in A and B to better compare the amplitude differences between normal and impaired mice. For routine threshold determinations, ABR were displayed in a relative scale adjusted to maximize the wave pattern for each stimulus as shown in C and D, because these wave patterns were more easily recognized thans when displayed in a fixed scale.

Fig. 2

ABR audiometric profiles for inbred strains with significant hearing impairment. For each strain and age of mice tested, ABR threshold values (in dB SPL) are plotted against the auditory stimulus frequency (in kHz). The normal hearing CBA/CaJ control strain is shown for comparison (A).