A mouse model for human hearing loss DFNB30 due to loss of function of myosin IIIA |
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Authors: | Vanessa L. Walsh Dorith Raviv Amiel A. Dror Hashem Shahin Tom Walsh Moien N. Kanaan Karen B. Avraham Mary-Claire King |
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Affiliation: | 1. Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA, 98195-7720, USA 2. Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel 3. Department of Biological Sciences, Bethlehem University, Bethlehem, Palestinian Authority
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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. |
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