• Yuta Seki, Hiroshi Shitara, Rie Ishii, Takafumi Ouchi, Shumpei P Yasuda, and Yoshiaki Kikkawa.
• Deafness Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
• Neuroscience. 2021 Dec 1; 478: 100-111.

AbstractIn human, myosin VI (MYO6) haploinsufficiency causes postlingual progressive hearing loss. Because the usefulness of mouse models remains unclear, we produced novel Myo6 null (-/-) mutant mice and analyzed the hearing phenotypes of Myo6+/- (+/-) heterozygous mutants. We first recorded and compared the auditory brainstem responses and distortion product otoacoustic emissions in control Myo6+/+ (+/+) wild-type and +/- mice. These hearing phenotypes of +/- mice were mild; however, we confirmed that +/- mice developed progressive hearing loss. In particular, the hearing loss of female +/- mice progressed faster than that of male +/- mice. The stereocilia bundles of +/- mice exhibited progressive taper loss in cochlear inner hair cells (IHCs) and outer hair cells (OHCs). The loss of OHCs in +/- heterozygotes occurred at an earlier age than in +/+ mice. In particular, the OHCs at the basal area of the cochlea were decreased in +/- mice. IHC ribbon synapses from the area at the base of the cochlea were significantly reduced in +/- mice. Thus, our study indicated that MYO6 haploinsufficiency affected the detection of sounds in mice, and we suggest that +/- mice with Myo6 null alleles are useful animal models for gene therapy and drug treatment in patients with progressive hearing loss due to MYO6 haploinsufficiency.Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

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