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，其特征是先天性耳聋，由于感觉毛细胞的丧失，以及由于视网膜色素变性导致的进行性视网膜变性。尽管迄今为止已经确定了导致Usher综合征的9个基因和1个基因修饰基因，但我们仍然缺乏对这些基因正常功能的了解，也不知道这种疾病中哪里出了问题。这主要是因为已知的10个基因编码的蛋白质种类非常广泛，而且都有多种同种异构体，而我们目前缺乏动物模型和工具来研究它们的功能。由于斑马鱼基因技术的最新进展，现在可以分离任何基因的突变，并且很容易产生具有改变基因表达的转基因动物。该项目将建立突变、转基因和抗体的文库，以表征所有已知的导致Usher综合征的基因。总之，这些文库将提供有史以来产生的第一个资源，以剖析构成人类疾病的整套已知基因的不同功能。

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.