Resource to support Usher syndrome research

支持亚瑟综合症研究的资源

基本信息

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
项目类别：
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

项目摘要

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）：由于感觉毛细胞的丧失而导致的，由于视网膜炎，人类的聋失明原因是聋失明的最常见原因，其特征是先天性耳聋。尽管迄今已鉴定出负责Usher综合征和一个遗传修饰剂基因的九个基因，但我们仍然缺乏对这些基因的正常功能或疾病中出问题的理解。这主要是因为十个已知的基因编码具有多种同工型的不同类型蛋白质的范围令人惊讶的广泛，我们目前缺乏动物模型和研究其功能的工具。由于斑马鱼遗传技术的最新进展，现在可以在任何基因中分离突变，并容易产生具有改变基因表达的转基因动物。该项目将开发突变体，转基因和抗体的库，以表征所有已知有助于usher综合征的基因。这些图书馆将共同提供有史以来第一个剖析人类疾病基础的已知基因的独特功能的资源。公共卫生相关性（由申请人提供）：Usher综合征是聋哑人的主要原因，是一种影响成千上万美国人的遗传疾病。至少十几个不同基因中的任何一个中的突变都可能引起usher综合征，但是导致听力和视力丧失的过程尚不清楚。该项目将开发出必要的动物模型和工具的完整资源，以了解Usher综合征的分子和细胞生物学。