The Genetics of Variation of the Wave 1 Amplitude of the Mouse Auditory Brainstem Response
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JARO (2020) DOI: 10.1007/s10162-020-00762-3 D 2020 Association for Research in Otolaryngology
Research Article
Journal of the Association for Research in Otolaryngology
The Genetics of Variation of the Wave 1 Amplitude of the Mouse Auditory Brainstem Response ELY CHEIKH BOUSSATY,1 DANIELLE GILLARD,1 JOEL LAVINSKY,2 PEZHMAN SALEHI,3 JUEMEI WANG,4 ALINE MENDONÇA,2 HOOMAN ALLAYEE,5 URI MANOR,6 AND RICK ADAM FRIEDMAN7 1
Department of Surgery, Division of Otolaryngology, University of California, San Diego, 9500 Gilman Drive, Mail Code 0666, La Jolla, CA 92093, USA 2
Federal University of Rio Grande do Sul, Sarmento Leite Street, 500 -, Porto Alegre, 90035-190, Brazil Northeast Ohio Medical University, 4209 OH-44, Rootstown, OH 44272, USA
3 4
University of Southern California, 1501 San Pablo St, Los Angeles, CA 90033, USA University of Southern California, 1975 Zonal Ave, Los Angeles, CA 90033, USA
5 6
Waitt Advanced Biophotonics Core, Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA
7
University of California, San Diego, 9444 Medical Center Drive, Mail Code 0768 -, La Jolla, CA 92037, USA
Received: 9 September 2019; Accepted: 19 July 2020
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 postexposure 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 Correspondence to: Rick Adam Friedman & University of California, San Diego & 9444 Medical Center Drive, Mail Code 0768 -, La Jolla, CA 92037, USA. email: [email protected]
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 G 1.12E-06) and chromosome 16 (16 kHz; JAX00424604; p G 9.02E-07) prior to noise exposure and significant associations on chromosomes 2 (32 kHz;
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