P23H Rhodopsin Mutant Swine Model of Reninitis Pigmentosa

P23H视紫红质突变猪色素性肾炎模型

基本信息

批准号：
8204540
负责人：
HENRY Jerrold KAPLAN
金额：
$ 18.59万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-12-01 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8204540
关键词：
Adult Age Animal Model Area Artificial Insemination Biomedical Engineering Blindness Cells Characteristics Clinical Communities Congenital Abnormality Data Disadvantaged Disease Disease Progression Exhibits Extinction (Psychology)Eye Family suidae Future Genetic Haplotypes Heterogeneity Histologic Histology Human Image Inbreeding Inheritance Patterns Inherited Life Methods Miniature Swine Missouri Modeling Molecular Abnormality Morphology Mutation Nuclear Peripheral Pharmacology Phenotype Photography Population Positioning Attribute Principal Investigator Research Project Grants Resources Retinal Retinal Cone Retinal Degeneration Retinitis Pigmentosa Rhodopsin Severities Site Therapeutic Therapeutic Intervention Time Transgenes Transgenic Organisms Translational Research Translations United States National Institutes of Health Universities Vision Visual Western World Work base clinical phenotype gene therapy innovation insight light microscopy male man mutant neurotrophic factor novel therapeutic intervention nuclear transfer offspring photoreceptor degeneration prevent programs reconstitution relating to nervous system research study retinal prosthesis retinal regeneration retinal rods somatic cell nuclear transfer stem cell therapy transmission process treatment effect

项目摘要

DESCRIPTION (provided by applicant): Retinal degeneration is a leading cause of blindness in the Western world and retinitis pigmentosa (RP) is the most common cause of hereditary visual loss in adult life. Although the genetic basis of RP has been well explored, the translation of this insight into successful genetic therapy has been hindered because of the mutational heterogeneity that underlies this group of diseases. In addition to gene therapy, we and others are exploring alternative therapeutic approaches employing recent advances in stem cell therapy, as well as the retinal prosthesis, bioengineering and pharmacology. Together these hold the promise for successful neural reconstitution in RP. Using the method of single cell nuclear transfer, we produced six male miniature swine (mini-swine) on a NIH cc haplotype carrying a mutant Pro23His (P23H) human rhodopsin transgene at the National Swine Resource Research Center at the University of Missouri-Columbia. Our preliminary data show that these founders exhibited an electrophysiologic phenotype characteristic of RP. Since P23H is the most common autosomal dominant mutation responsible for RP in man, we propose to establish a colony and characterize three independent transgenic lines of this new mini-swine model of photoreceptor degeneration. While outside the time frame of this application, in the near future it can be used by us and the vision community for novel therapeutic interventions. PUBLIC HEALTH RELEVANCE: Using the method of single cell nuclear transfer, we produced six male miniature swine (mini-swine) on a NIH cc haplotype carrying a mutant Pro23His (P23H) human rhodopsin transgene at the National Swine Resource Research Center at the University of Missouri-Columbia. Our preliminary data show that these founders exhibited an electrophysiologic phenotype characteristic of retinitis pigmentosa (RP). Since P23H is the most common autosomal dominant mutation responsible for RP in humans, we propose to establish a colony and characterize three independent transgenic lines of this new mini-swine model of photoreceptor degeneration for future therapeutic interventions.

描述（由申请人提供）：视网膜变性是西方世界失明的主要原因，色素性视网膜炎（RP）是成人生活中遗传性视觉丧失的最常见原因。尽管对RP的遗传基础进行了充分的探索，但由于突变的异质性是基于该疾病的突变异质性，因此将这种洞察力转化为成功的基因治疗。除基因疗法外，我们和其他人还在探索采用干细胞疗法以及视网膜假体，生物工程和药理学的最新进展的替代治疗方法。这些共同有望在RP中成功进行神经重建。使用单细胞核转移方法，我们在密苏里州哥伦比亚大学国家猪资源研究中心的NIH CC单倍型上生产了六只雄性微型猪（迷你 - 酮）。我们的初步数据表明，这些创始人表现出RP的电生理表型特征。由于p23h是负责人中RP的最常见常染色体显性突变，因此我们建议建立一个菌落，并表征这种新型的感光受体变性的新型迷你酮模型的三个独立的转基因线。在此应用程序的时间范围之外，在不久的将来，它可以被我们和新型治疗干预措施的视觉社区使用。公共卫生相关性：使用单细胞核转移的方法，我们在NIH CC单倍型上生产了六只男性微型猪（迷你 - 酮），该型含有突变体Pro23His（p23h）的人类肖陶蛋白转基因在国家国家猪资源研究中心密苏里州哥伦比亚。我们的初步数据表明，这些创始人表现出色素性视网膜炎（RP）的电生理表型。由于P23H是负责人类RP的最常见的常染色体显性突变，因此我们建议建立一个菌落，并表征这种新型的感光受体变性的新型迷你旋转模型的三个独立的转基因线，以实现未来的治疗干预措施。