Studies of genetic disorders of sensorineural hearing loss have been instrumental in delineating mechanisms that underlie the remarkable sensitivity and selectivity that are hallmarks of mammalian hearing. For example, genetic modifications of TECTA and TECTB, which are principal proteins that comprise the tectorial membrane (TM), have been shown to alter auditory thresholds and frequency tuning in ways that can be understood in terms of changes in the mechanical properties of the TM. Here, we investigate effects of genetic modification targeting CEACAM16, a third important TM protein. Loss of CEACAM16 has been recently shown to lead to progressive reductions in sensitivity. Whereas age-related hearing losses have previously been linked to changes in sensory receptor cells, the role of the TM in progressive hearing loss is largely unknown. Here, we show that TM stiffness and viscosity are significantly reduced in adult mice that lack functional CEACAM16 relative to age-matched wild-type controls. By contrast, these same mechanical properties of TMs from juvenile mice that lack functional CEACAM16 are more similar to those of wild-type mice. Thus, changes in hearing phenotype align with changes in TM material properties and can be understood in terms of the same TM wave properties that were previously used to characterize modifications of TECTA and TECTB. These results demonstrate that CEACAM16 is essential for maintaining TM mechanical and wave properties, which in turn are necessary for sustaining the remarkable sensitivity and selectivity of mammalian hearing with increasing age.

对感音神经性听力损失遗传性疾病的研究有助于阐明哺乳动物听力标志性的显着敏感性和选择性的机制。例如，TECTA 和 TECTB（构成盖膜 (TM) 的主要蛋白质）的基因修饰已被证明可以改变听觉阈值和频率调谐，这种方式可以通过 TM 机械特性的变化来理解。 。在这里，我们研究了针对第三个重要 TM 蛋白 CEACAM16 的基因改造的影响。最近显示，CEACAM16 的缺失会导致敏感性逐渐降低。虽然年龄相关的听力损失之前被认为与感觉感受器细胞的变化有关，但 TM 在进行性听力损失中的作用在很大程度上尚不清楚。在这里，我们发现，相对于年龄匹配的野生型对照，缺乏功能性 CEACAM16 的成年小鼠的 TM 硬度和粘度显着降低。相比之下，缺乏功能性 CEACAM16 的幼年小鼠的 TM 的机械特性与野生型小鼠更相似。因此，听力表型的变化与 TM 材料特性的变化一致，并且可以根据先前用于表征 TECTA 和 TECTB 修改的相同 TM 波特性来理解。这些结果表明，CEACAM16 对于维持 TM 机械和波特性至关重要，而这反过来又是维持哺乳动物听力随着年龄增长而显着的敏感性和选择性所必需的。