Resource to support Usher syndrome research

描述（由申请人提供）：人类Usher综合征是聋盲的最常见原因，其特征是由于感觉毛细胞丧失引起的先天性耳聋和由于色素性视网膜炎引起的进行性视网膜变性。尽管迄今为止已经确定了9个导致Usher综合征的基因和1个遗传修饰基因，但我们仍然缺乏对这些基因的正常功能或疾病中出现的问题的了解。这主要是因为这10个已知基因编码的蛋白质种类之多令人惊讶，而且都有多种亚型，而我们目前缺乏动物模型和工具来研究它们的功能。由于斑马鱼遗传技术的最新进展，现在可以分离任何基因中的突变并容易地产生具有改变的基因表达的转基因动物。该项目将开发突变体，转基因和抗体库，以表征已知导致Usher综合征的所有基因。总之，这些文库将提供有史以来第一个资源，以剖析构成人类疾病基础的全套已知基因的独特功能。

DESCRIPTION (provided by applicant): Human Usher syndrome, the most frequent cause of deaf blindness, is characterized by congenital deafness, due to loss of sensory hair cells, and progressive retinal degeneration, due to retinitis pigmentosa. Although nine of the genes responsible for Usher syndrome and one genetic modifier gene have been identified to date, we still lack an understanding of the normal functions of these genes or what goes wrong in the disease. This is primarily because the ten known genes encode a surprisingly broad range of different types of proteins, all with multiple isoforms, and we currently lack animal models and tools to study their functions. Due to recent advances in zebrafish genetic technology, it is now possible to isolate mutations in any gene and easily produce transgenic animals with altered gene expression. This project will develop libraries of mutants, transgenics, and antibodies to characterize all the genes known to contribute to Usher syndrome. Together, these libraries will provide the first resource ever generated to dissect the distinct functions of the complete set of known genes that underlie a human disease.