title: A mouse model for human hearing loss DFNB30 due to loss of function of myosin IIIA.
abstract: The motor protein myosin IIIA is critical for maintenance of normal hearing. Homozygosity and compound heterozygosity for loss-of-function mutations in MYO3A, which encodes myosin IIIA, are responsible for inherited human progressive hearing loss DFNB30. To further evaluate this hearing loss, we constructed a mouse model, Myo3a(KI/KI), that harbors the mutation equivalent to the nonsense allele responsible for the most severe human phenotype. Myo3a(KI/KI) mice were compared to their wild-type littermates. Myosin IIIA, with a unique N-terminal kinase domain and a C-terminal actin-binding domain, localizes to the tips of stereocilia in wild-type mice but is absent in the mutant. The phenotype of the Myo3a(KI/KI) mouse parallels the phenotype of human DFNB30. Hearing loss, as measured by auditory brainstem response, is reduced and progresses significantly with age. Vestibular function is normal. Outer hair cells of Myo3a(KI/KI) mice degenerate with age in a pattern consistent with their progressive hearing loss.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195-7720, USA.
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Walsh
authors.forename: Dorith
authors.initials: D
authors.lastname: Raviv
authors.forename: Amiel A
authors.initials: AA
authors.lastname: Dror
authors.forename: Hashem
authors.initials: H
authors.lastname: Shahin
authors.forename: Tom
authors.initials: T
authors.lastname: Walsh
authors.forename: Moien N
authors.initials: MN
authors.lastname: Kanaan
authors.forename: Karen B
authors.initials: KB
authors.lastname: Avraham
authors.forename: Mary-Claire
authors.initials: MC
authors.lastname: King
mesh_terms: D000367:Age Factors; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D034381:Hearing Loss / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D025102:Myosin Type III / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D017434:Protein Structure, Tertiary
chemical_list: C558785:MYO3A protein, mouse; D025102:Myosin Type III; D018995:Myosin Heavy Chains