Resource to support Usher syndrome research

支持亚瑟综合症研究的资源

• 批准号: 8181474
• 负责人: Monte Westerfield
• 金额: $ 31.63万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-14 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8181474
• 关键词: Affect; Alleles; American; Animal Model; Antibodies; Biological Assay; Blindness; Cells; Cloning; Code; Communities; Deposition; Development; Disease; Ear; Engineering; Enhancers; Eye; Gene Expression; Gene Mutation; Gene Targeting; Genes; Genetic; Genetic Recombination; Hair Cells; Hearing Impaired Persons; Hereditary Disease; Human; Information Centers; International; Labyrinth; Lead; Libraries; Molecular and Cellular Biology; Mutate; Mutation; Mutation Analysis; Neuroglia; Neurons; Orthologous Gene; Pathology; Physiology; Principal Investigator; Process; Protein Isoforms; Protein Region; Proteins; Research; Resources; Retina; Retinal Degeneration; Retinitis Pigmentosa; Sensory Hair; Site; System; Techniques; Terminator Codon; Transgenes; Transgenic Animals; Transgenic Organisms; Usher Syndrome; Validation; Vision; Zebrafish; Zinc Fingers; animal resource; cell type; congenital deafness; gene function; genetic technology; hearing impairment; human disease; loss of function; loss of function mutation; model organisms databases; mutant; nuclease; promoter; tool; vector

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. PUBLIC HEALTH RELEVANCE (provided by applicant): Usher syndrome, the leading cause of deaf blindness, is a genetic disorder that affects tens of thousands of Americans. Mutations in any one of at least a dozen different genes can cause Usher syndrome, but the processes that lead to loss of hearing and vision are unknown. This project will develop a complete resource of animal models and tools necessary to understand the molecular and cellular biology of Usher syndrome.

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。 公共卫生相关性（由申请人提供）：Usher综合征是导致聋盲的主要原因，是一种影响数万美国人的遗传性疾病。至少十几种不同基因中的任何一种突变都可能导致Usher综合征，但导致听力和视力丧失的过程尚不清楚。这个项目将开发一个完整的资源，动物模型和必要的工具，以了解分子和细胞生物学的Usher综合征。