Department of Medicine, University of Washington, Seattle, WA 98195-7720, USA.
Mamm Genome. 2011 Apr;22(3-4):170-7. doi: 10.1007/s00335-010-9310-6. Epub 2010 Dec 17.
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.
肌球蛋白 IIIA 是维持正常听力所必需的。编码肌球蛋白 IIIA 的 MYO3A 基因的纯合子和复合杂合子缺失功能突变，导致遗传性进行性听力损失 DFNB30。为了进一步评估这种听力损失，我们构建了一个携带与导致最严重人类表型的无义等位基因等效突变的小鼠模型 Myo3a(KI/KI)。Myo3a(KI/KI) 小鼠与它们的野生型同窝仔进行了比较。肌球蛋白 IIIA 具有独特的 N 端激酶结构域和 C 端肌动蛋白结合结构域，在野生型小鼠中定位于静纤毛的尖端，但在突变体中不存在。Myo3a(KI/KI) 小鼠的表型与人类 DFNB30 的表型相似。通过听觉脑干反应测量的听力损失减少，并随年龄显著进展。前庭功能正常。Myo3a(KI/KI) 小鼠的外毛细胞随年龄退化，与进行性听力损失的模式一致。
