Myosin VI Haploinsufficiency Reduced Hearing Ability in Mice. (1st December 2021)

• Record Type: Journal Article
• Authors: Seki, Yuta; Shitara, Hiroshi; Ishii, Rie; Ouchi, Takafumi; Yasuda, Shumpei P.; Kikkawa, Yoshiaki
• Is Part Of: Neuroscience. Volume 478(2021)
• Page Start: 100
• Page End: 111
• Publication Date: 2021-12-01
• Subjects: 2D two-dimensional -- 3D three-dimensional -- ABR auditory brainstem response -- ahl (Cdh23ahl) age-related hearing loss allele of cadherin 23 gene -- ANOVA analysis of variance -- AP-2 adaptor protein 2 -- ARHL age-related hearing loss -- C57BL/6J C57BL/6JJcl -- Cdh23 cadherin 23 -- CRISPR/Cas9 clustered regularly interspaced short palindromic repeat-associated Cas9 nuclease -- CtBP2 C-terminal binding protein 2 -- DFNA nonsyndromic deafness, autosomal dominant -- DFNB nonsyndromic deafness, autosomal recessive -- DFNX nonsyndromic deafness, X-linked -- DPOAE distortion product otoacoustic emission -- EDTA ethylenediaminetetraacetic acid -- IHC inner hair cell -- MYO6 myosin VI -- Myo6sv Snell's waltzer -- NA numerical aperture -- NSHL nonsyndromic hearing loss -- OHC outer hair cell -- OTOF otoferlin -- p.T13Mfs15* "prefix" "amino acid (threonine)" "position 13" new amino acid (methionine)" "frameshift" "position termination site (15)" "termination codon" -- SD standard deviation -- SEM scanning electron microscopy -- STED stimulated emission depletion microscopy; myosin VI -- haploinsufficiency -- hearing loss -- stereocilia -- cochlear hair cell -- ribbon synapse; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2021.09.023
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Myosin VI haploinsufficiency leads to mild hearing loss in mice. Heterozygous myosin VI knockout mice developed age-related stereocilia fusion. The outer hair cells of aged mice decreased due to myosin VI haploinsufficiency. The ribbon synapses of aged mice were decreased due to myosin VI haploinsufficiency. Abstract: In 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.