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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Essential role of retinoblastoma protein in mammalian hair cell development and hearing
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Essential role of retinoblastoma protein in mammalian hair cell development and hearing

机译：视网膜母细胞瘤蛋白在哺乳动物毛细胞发育和听力中的重要作用

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The retinoblastoma protein pRb is required for cell-cycle exit of embryonic mammalian hair cells but not for their early differentiation. However, its role in postnatal hair cells is unknown. To study the function of pRb in mature animals, we created a new conditional mouse model, with the Rb gene deleted primarily in the inner ear. Progeny survive up to 6 months. During early postnatal development, pRb(-/-) hair cells continue to divide and can transduce mechanical stimuli. However, adult pRb(-/-) mice exhibit profound hearing loss due to progressive degeneration of the organ of Corti. We show that pRb is required for the full maturation of cochlear outer hair cells, likely in a gene-specific manner, and is also essential for their survival. In addition, lack of pRb results in cell division in postnatal auditory supporting cells. In contrast, many pRb(-/-) vestibular hair cells survive and continue to divide in adult mice. Significantly, adult pRb(-/)- vestibular hair cells are functional, and pRb(-/-) mice maintain partial vestibular function. Therefore, the functional adult vestibular pRb(-/-) hair cells, derived from proliferation of postnatal hair cells, are largely integrated into vestibular pathways. This study reveals essential yet distinct roles of pRb in cochlear and vestibular hair cell maturation, function, and survival and suggests that transient block of pRb function in mature hair cells may lead to propagation of functional hair cells.
机译：视网膜母细胞瘤蛋白pRb是胚胎哺乳动物毛细胞的细胞周期退出所必需的，而不是其早期分化所需的。但是，其在产后毛细胞中的作用尚不清楚。为了研究pRb在成熟动物中的功能，我们创建了一个新的条件小鼠模型，其中Rb基因主要在内耳缺失。后代最多可以存活6个月。在出生后早期发育期间，pRb（-/-）毛细胞继续分裂并可以转导机械刺激。但是，成年的pRb（-/-）小鼠由于Corti器官的逐渐退化而表现出严重的听力损失。我们表明，pRb是可能完全以基因特异性的方式进行的人工耳蜗外毛细胞的完全成熟所必需的，并且pRb对于它们的生存也是必不可少的。此外，缺乏pRb会导致产后听觉支持细胞分裂。相反，许多pRb（-/-）前庭毛细胞在成年小鼠中存活并继续分裂。重要的是，成年pRb（-/）-前庭毛细胞具有功能，而pRb（-/-）小鼠则保持部分前庭功能。因此，源于产后毛细胞增殖的功能性成人前庭pRb（-/-）毛细胞在很大程度上整合到了前庭通路中。这项研究揭示了pRb在耳蜗和前庭毛细胞成熟，功能和存活中的重要但又不同的作用，并表明pRb在成熟毛细胞中的暂时性阻滞可能导致功能性毛细胞的繁殖。

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