The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
Mamm Genome. 2011 Apr;22(3-4):156-69. doi: 10.1007/s00335-010-9309-z. Epub 2010 Dec 15.
The inner ear consists of the cochlea (the organ of hearing) and the vestibular system (the organs of balance). Within the vestibular system, linear acceleration and gravity are detected by the saccule and utricle. Resting above the neurosensory epithelia of these organs are otoconia, minute proteinaceous and crystalline (calcite) inertial masses that shift under the physical forces imparted by linear movements and gravity. It is the transduction and sensation of these movements and their integration with vision and proprioceptive inputs that contribute to the sensation of balance. It has been proposed that a reactive oxygen species- (ROS-) generating NADPH oxidase comprising the gene products of the Nox3, Noxo1, and Cyba genes plays a critical and constructive role in the process of inner-ear development, specifically, the deposition of otoconia. Inactivation in mouse of any of the NADPH oxidase components encoded by the Nox3, Noxo1, or Cyba gene results in the complete congenital absence of otoconia and profound vestibular dysfunction. Here we describe our use of PCR, reverse transcription-PCR (RT-PCR), and rapid amplification of cDNA ends (RACE) with traditional and high-throughput (HTP) sequencing technologies to extend and complete the molecular characterization of an allelic series of seven mutations in the Nox3 gene. Collectively, the mutation spectrum includes an endogenous retrovirus insertion, two missense mutations, a splice donor mutation, a splice acceptor mutation, premature translational termination, and a small duplication. Together, these alleles provide tools to investigate the mechanisms of otoconial deposition over development, throughout aging, and in various disease states.
内耳包括耳蜗（听觉器官）和前庭系统（平衡器官）。在前庭系统中，囊斑和椭圆囊检测到线性加速度和重力。在这些器官的神经感觉上皮上方是耳石，微小的蛋白和结晶（方解石）惯性质量，在线性运动和重力施加的物理力作用下会发生移位。正是这些运动的转导和感觉及其与视觉和本体感觉输入的整合，导致了平衡感。有人提出，一种由 Nox3、Noxo1 和 Cyba 基因的产物组成的产生活性氧物质（ROS）的 NADPH 氧化酶在内耳发育过程中起着关键和建设性的作用，特别是耳石的沉积。在小鼠中，任何由 Nox3、Noxo1 或 Cyba 基因编码的 NADPH 氧化酶成分失活都会导致耳石完全先天性缺失和严重的前庭功能障碍。在这里，我们使用 PCR、逆转录 PCR（RT-PCR）和快速扩增 cDNA 末端（RACE）技术，结合传统和高通量（HTP）测序技术，扩展和完成了 Nox3 基因的一个等位基因系列的七个突变的分子特征描述。总的来说，该突变谱包括一个内源性逆转录病毒插入、两个错义突变、一个剪接供体位点突变、一个剪接受体位点突变、提前翻译终止和一个小的重复。这些等位基因共同为研究耳石沉积在发育过程中的机制、整个衰老过程以及在各种疾病状态下的机制提供了工具。
