The Mouse Auditory Testing (MAT) Core facility assists NIDCD investigators and their collaborators with auditory and vestibular function testing in mice. Two physiological measures of auditory function are employed at the MAT Core: the auditory brainstem response (ABR) and distortion-product otoacoustic emissions (DPOAEs). The ABR is an evoked potential that can be used to estimate hearing thresholds. DPOAEs are soft sounds that are recorded in the ear canal using a small microphone. DPOAEs can be used to screen for hearing loss and to evaluate inner ear function; specifically, the presence of DPOAEs indicates normal function of outer hair cells in the inner ear. The facility also assists with noise exposure protocols. Vestibular sensory evoked potentials (VsEPs) are measured to assess vestibular function in mice. VsEPs are recorded by placing electrodes on the scalp and recording the electrical potentials generated by the vestibular nervous system in response to linear movements of the head. Normative data collection and the first experimental data collection using the VsEP system were completed this year under the direction of Dr. Talah Wafa (Post-Doctoral Fellow). This past year, otoscopy and tympanometry/wide-band absorbance tests were added to the available test battery for auditory function testing and began limited use. Otoscopy with a surgical microscope allows visualization of the pinna, external auditory canal, and tympanic membrane for signs of pathology. Tympanometry and wide-band absorbance measures assess middle-ear function. Dr. Fitzgerald began or continued training in auditory function testing with 13 NIDCD investigators. Dr. Wafa began training seven NIDCD investigators in vestibular function testing. Seven investigators completed auditory function testing independently but received support from the MAT Core. Dr. Fitzgerald continued training/consultation in auditory testing and data analyses with two investigators from other NIH Institutes (NIMH, NIA). Dr. Fitzgerald trained one investigator from outside the NIH (School of Medicine, University of Maryland-Baltimore) in auditory testing and data analyses. Dr. Fitzgerald collaborated on and/or supported 30 projects conducted in 8 NIDCD labs. Dr. Fitzgerald collaborated on two projects from labs in other NIH institutes (NIA, NIMH). Dr. Fitzgerald was a co-author on two manuscripts published this past year. Information on collaborations with specific laboratories is listed below. Inner Ear Gene Therapy Program (PI: Wade Chien, M.D.) Dr. Fitzgerald supported eleven projects investigating the use of gene therapy to remediate hearing loss. Dr. Fitzgerald trained Jianliang Zhu (Biologist) and in auditory function testing and data analyses and provided support to Kevin Isgrig (Biologist) and Dr. Hong Jun Wang (Staff Scientist). Section on Sensory Cell Biology (PI: Lisa Cunningham, Ph.D.) Dr. Fitzgerald assisted with initial training of Ben Gersten (Post-Bac IRTA) and Erica Sadler (Post-Bac IRTA) in auditory function testing and data analyses. Dr. Fitzgerald provided support to Dr. Katharine Fernandez (Staff Scientist) and Ben Gersten for three projects aimed at the prevention of Cisplatin ototoxicity. Section on Genetics of Communication Disorders (PI: Dennis Drayna, Ph.D.) Dr. Fitzgerald consulted with Tae-Un Han (Research Fellow) and Dr. Drayna on noise exposures for a project on mutant mice. Laboratory of Molecular Genetics (PI: Thomas Friedman, Ph.D.) Dr. Fitzgerald collaborated on seven projects examining auditory and/or vestibular function in various mutant mouse strains, including projects with Dr. Inna Belyantseva (Staff Scientist), Dr. Jonathan Bird (Former Post-Doctoral Fellow), Dr. Melanie Barzik (Staff Scientist), Dr. Ayesha Imtiaz (Post-Doctoral Visiting Fellow), and Dr. Risa Tona (Post-Doctoral Visiting Fellow). Dr. Fitzgerald assisted Dr. Robert Morell (Director, Genomics and Computational Biology Core) with three projects investigating auditory function in mutant mice. Dr. Fitzgerald assisted with set-up and calibration of noise exposure experiments. Dr. Fitzgerald began training in auditory function testing with Wenqian Chen (Post-Bac IRTA) and Sam Leitess (Post-Bac IRTA). Dr. Fitzgerald provided continued training and/or support to Rabia Faridi (Pre-Doctoral Visiting Fellow), Randall Harley (Post-Bac IRTA), Connor Hill (Post-Bac IRTA), Risa Tona, Kerianne Richards (Contractor Bioinformatics, Genomics and Computational Biology Core) and Elizabeth Wilson Bernhard (Biologist). Dr. Wafa began training Wenqian Chen and Risa Tona in vestibular function testing and data analysis. Dr. Fitzgerald and Elizabeth Wilson Bernhard continued work on a survey of auditory sensitivity with age in the Friedman lab C57Bl6J and B6.CAST-Cdh23 Ahl+/Kjn mice. Dr. Fitzgerald assisted with one published manuscript and one manuscript still in preparation. Section on Molecular Biology and Genetics (PI: Andrew Griffith, M.D., Ph.D.) Dr. Fitzgerald trained Danielle Harrow (Biologist) in tympanometry and collaborated on and/or supported two projects examining auditory function in mutant mice. Dr. Fitzgerald assisted with preparation of a one published manuscript. Section on Structural Cell Biology (PI: Bechara Kachar, Ph.D.) Dr. Fitzgerald trained Dr. Mhamad Grati (Staff Scientist), Willy Sun (Pre-Doctoral IRTA Fellow), and Runjia Cui (Contractor) in auditory testing and data analyses for a project examining auditory function in mutant mice. Dr. Wafa began training Dr. Grati, Mr. Sun, and Ms. Cui in vestibular function testing and data analysis for the same project. Laboratory of Cochlear Development (PI: Matthew Kelley, Ph.D.) Dr. Fitzgerald trained Helen Maunsell (Post-Bac IRTA) in auditory testing and data analyses for two projects investigating mutant mice. Section on Sensory Cell Regeneration and Development (PI: Doris Wu, Ph.D.) Dr. Wafa and Dr. Fitzgerald began training Dr. Kazuya Ono (Post-Doctoral Visiting Fellow) and Dr. Yosuke Tona (Post-Doctoral Visiting Fellow) in vestibular function testing and data analyses for two projects on mutant mice. Laboratory of Molecular Gerontology, NIA (PI: Vilhelm Bohr, M.D., Ph.D.) Dr. Fitzgerald continued training and consulting with M. Nazir Okur (Post-Doctoral Fellow) in auditory function testing and data analyses for a project on a mouse model of Cockayne Syndrome (CS) conducted in collaboration with the Kelley Lab. Unit on Neural Circuits and Adaptive Behaviors, NIMH (PI: Kaun Hong Wang, Ph.D.) Dr. Fitzgerald continued training with and supported Fhatarah Zinnamon (NIMH-UCL GPP Program IRTA Fellow) for her project examining auditory function in Df1/+ mice. In July 2018, the MAT Core participated in the annual Earssentials workshop, a week-long course designed to expose new trainees to auditory research at the NIDCD through lectures and laboratory exercises. Twelve students participated in a laboratory training exercise on auditory testing in mice given by Dr. Fitzgerald, Elizabeth Wilson Bernhard, and Dr. Katharine Fernandez.

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Budget End
Support Year
7
Fiscal Year
2018
Total Cost
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Name
Deafness & Other Communication Disorders
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Nakanishi, Hiroshi; Kurima, Kiyoto; Pan, Bifeng et al. (2018) Tmc2 expression partially restores auditory function in a mouse model of DFNB7/B11 deafness caused by loss of Tmc1 function. Sci Rep 8:12125
Imtiaz, Ayesha; Belyantseva, Inna A; Beirl, Alisha J et al. (2018) CDC14A phosphatase is essential for hearing and male fertility in mouse and human. Hum Mol Genet 27:780-798
Bird, Jonathan E; Barzik, Melanie; Drummond, Meghan C et al. (2017) Harnessing molecular motors for nanoscale pulldown in live cells. Mol Biol Cell 28:463-475
Breglio, Andrew M; Rusheen, Aaron E; Shide, Eric D et al. (2017) Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun 8:1654
Tran, Linda; Allen, Clint T; Xiao, Roy et al. (2017) Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma. Cancer Immunol Res 5:1141-1151
Isgrig, Kevin; Shteamer, Jack W; Belyantseva, Inna A et al. (2017) Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome. Mol Ther 25:780-791
Nishio, Ayako; Ito, Taku; Cheng, Hui et al. (2016) Slc26a4 expression prevents fluctuation of hearing in a mouse model of large vestibular aqueduct syndrome. Neuroscience 329:74-82
Chien, Wade W; McDougald, Devin S; Roy, Soumen et al. (2015) Cochlear gene transfer mediated by adeno-associated virus: Comparison of two surgical approaches. Laryngoscope :
Morozko, Eva L; Nishio, Ayako; Ingham, Neil J et al. (2015) ILDR1 null mice, a model of human deafness DFNB42, show structural aberrations of tricellular tight junctions and degeneration of auditory hair cells. Hum Mol Genet 24:609-24
Chien, Wade W; Isgrig, Kevin; Roy, Soumen et al. (2015) Gene therapy restores hair cell stereocilia morphology in inner ears of deaf whirler mice. Mol Ther :

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