1. The Genetics of Variation of the Wave 1 Amplitude of the Mouse Auditory Brainstem Response
- Author
-
Danielle M. Gillard, Rick A. Friedman, Hooman Allayee, Ely Cheikh Boussaty, Aline Mendonça, Uri Manor, Juemei Wang, Pezhman Salehi, and Joel Lavinsky
- Subjects
Candidate gene ,medicine.medical_specialty ,Audiology ,Biology ,01 natural sciences ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Chromosome 16 ,0103 physical sciences ,Evoked Potentials, Auditory, Brain Stem ,otorhinolaryngologic diseases ,medicine ,Animals ,010301 acoustics ,Genetic association ,Synaptic ribbon ,Hair Cells, Auditory, Inner ,Glutamate receptor ,Auditory Threshold ,Sensory Systems ,Auditory brainstem response ,Amplitude ,Otorhinolaryngology ,Chromosome 3 ,Female ,sense organs ,Noise ,030217 neurology & neurosurgery ,Genome-Wide Association Study ,Research Article - Abstract
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
- Published
- 2020