Cloning and Analysis of Head Tilt, A Vestibular Mutant

描述（由申请人提供）：复杂生物体感知 重力、运动和空间定向是一个关键的功能， 前庭系统拟议的研究将调查的分子基础， 一种小鼠突变头倾斜（het），它破坏了重力感受器的功能。 在初步研究中，这种突变体的病理学已经揭示了一个完整的 没有耳石，碳酸钙晶体刺激 前庭斑在直线加速和重力。这个的目标 应用程序简单明了，重点突出。我们打算分析het突变体 表型和克隆het基因，以了解其功能， 耳石发育拟议的研究旨在：1）完成 het-关键区，并鉴定和表征het基因; 2）进一步 通过组织学、电子显微镜和 胚胎干（ES）细胞方法;和3）分析耳锥维持使用 条件基因表达技术。这些实验将 更清楚地了解前庭功能和疾病。

DESCRIPTION (provided by applicant): The ability of complex organisms to sense gravity, motion, and spatial orientation is a crucial function enabled by the vestibular system. The proposed studies will investigate the molecular basis of a mouse mutation head tilt (het), which has disrupted gravity receptor function. In preliminary studies, the pathology of this mutant has revealed a complete absence of otoconia, the calcium carbonate crystals that stimulate the vestibular maculae during linear acceleration and gravity. The goals of this application are straightforward and focused. We intend to analyze the het mutant phenotype and to clone the het gene in order to understand its function in otolith development. The proposed studies aim to: 1) complete a physical map of the het-critical region and identify and characterize the het gene; 2) further characterize the het mutant phenotype by histological, electron microscopic, and embryonic stem (ES) cell approaches; and 3) analyze otoconial maintenance using conditional gene expression technologies. Together these experiments will provide a clearer understanding of vestibular function and disease.