The Genetics of Variation of the Wave 1 Amplitude of the Mouse Auditory Brainstem Response

This is the first genome-wide association study with the Hybrid Mouse Diversity Panel (HDMP) to define the genetic landscape of the variation in the suprathreshold wave 1 amplitude of the auditory brainstem response (ABR) both pre- and post-noise exposure. This measure is correlated with the density...

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Bibliographic Details
Published in:Journal of the Association for Research in Otolaryngology 2020-08, Vol.21 (4), p.323-336
Main Authors: Boussaty, Ely Cheikh, Gillard, Danielle, Lavinsky, Joel, Salehi, Pezhman, Wang, Juemei, Mendonça, Aline, Allayee, Hooman, Manor, Uri, Friedman, Rick Adam
Format: Article
Language:English
Subjects:
Association analysis
Brain stem
Chromosome 16
Chromosome 3
Cochlea
Genetic diversity
Genome-wide association studies
Genomes
Genomics
Glutamic acid receptors
Glutamic acid receptors (metabotropic)
Hair cells
Hearing
Hearing protection
Medicine
Medicine & Public Health
Neurobiology
Neurosciences
Noise
Otorhinolaryngology
Population structure
Research Article
Ribonucleic acid
RNA
Synaptic ribbons
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Summary:This is the first genome-wide association study with the Hybrid Mouse Diversity Panel (HDMP) to define the genetic landscape of the variation in the suprathreshold wave 1 amplitude of the auditory brainstem response (ABR) both pre- and post-noise exposure. This measure is correlated with the density of the auditory neurons (AN) and/or the compliment of synaptic ribbons within the inner hair cells of the mouse cochlea. We analyzed suprathreshold ABR for 635 mice from 102 HMDP strains pre- and post-noise exposure (108 dB 10 kHz octave band noise exposure for 2 h) using auditory brainstem response (ABR) wave 1 suprathreshold amplitudes as part of a large survey (Myint et al., Hear Res 332:113–120, 2016). Genome-wide significance levels for pre- and post-exposure wave 1 amplitude across the HMDP were performed using FaST-LMM. Synaptic ribbon counts (Ctbp2 and mGluR2) were analyzed for the extreme strains within the HMDP. ABR wave 1 amplitude varied across all strains of the HMDP with differences ranging between 2.42 and 3.82-fold pre-exposure and between 2.43 and 7.5-fold post-exposure with several tone burst stimuli (4 kHz, 8 kHz, 12 kHz, 16 kHz, 24 kHz, and 32 kHz). Immunolabeling of paired synaptic ribbons and glutamate receptors of strains with the highest and lowest wave 1 values pre- and post-exposure revealed significant differences in functional synaptic ribbon counts. Genome-wide association analysis identified genome-wide significant threshold associations on chromosome 3 (24 kHz; JAX00105429; p  
ISSN:1525-3961
1438-7573
DOI:10.1007/s10162-020-00762-3