MODELS OF HEREDITY RETINAL DEGENERATION

遗传性视网膜变性模型

• 批准号: 6045511
• 负责人: GREGORY M ACLAND
• 金额: $ 62.75万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-12-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6045511
• 关键词: animal breeding; animal colony; apoptosis; cell transplantation; cooperative study; disease /disorder model; dogs; gene mutation; gene therapy; genetic models; genetic strain; inborn biological transport disorder; model design /development; molecular cloning; nonhuman therapy evaluation; retina degeneration; retinal pigment epithelium; transfection; visual photoreceptor

DESCRIPTION: (Applicant's Abstract) This application's purpose is to make available to the research community certain canine strains affected with hereditary retinal degenerations, in order to facilitate research into the causes and cures of such diseases in people. This resource project, continuously managed by the principal investigators for the past 20 years, has 3 broad aspects. The first is to serve as a center for production and distribution, primarily to other independent research investigators, of 5 canine mutant models of hereditary retinal degenerations affecting humans. The need for these animals in research is addressed, as is the importance of maintaining them in a centralized breeding and distribution facility. The second objective is to continue collaborative studies already established to clone the genes for these diseases, investigate the cellular and molecular biology of these diseases, and develop methods for therapeutic intervention. The third aspect is to make available the physical and personnel resources supported by this project for instituting and conducting therapeutic trials as initiated by independent research investigators, either from academic or industrial organizations. Each such collaborative study is peer reviewed, separately, as part of the collaborative investigators' research protocols. Five strains of dogs, each transmitting a different gene for well characterized hereditary retinal degenerations (rod-cone dysplasia type 1 rcdl, progressive rod-cone degeneration prcd, early retinal degeneration erd, cone degeneration cd, and the newly available RPE65 mutant dog strain), together with appropriate nonaffected control dogs, will be bred and maintained. The progeny of these dogs will be distributed to research investigators, either directly or by collection, processing and distribution of requested tissues. Utilization of these mutants will be promoted by solicitation of requests from investigators. Assistance will be offered to investigators in development and implementation of specific protocols for optimal utilization of these mutants. Specific collaborative research includes programs to: identify, clone, and characterize the gene in cd, erd, prcd, and rcdl; cd, erd and prcd; determine and compare the role of programmed cell death genes in cd, erd, prcd, and rcdl; define the cause of abnormalities in docosaehexanoic acid transport & metabolism in prcd and identify candidate genes responsible for these deficiencies; further develop therapies for hereditary retinal degenerations including vector mediated gene transfer into canine photoreceptors; photoreceptor and retinal pigment epithelial cell transplantation into canine retina; and application of a visual-prosthetic silicon chip retinal implant.

描述：（申请人的摘要）此申请的目的是使 可用于研究社区的某些受影响的犬菌株 遗传性视网膜变性，以促进研究 这种疾病中这种疾病的原因和治愈。这个资源项目， 在过去的20年中，由主要研究人员不断管理， 3个广泛的方面。首先是作为生产中心和 分配，主要分配给其他独立研究研究者，有5个 遗传性视网膜变性的犬类突变模型影响人类。这 在研究中需要这些动物的需求，以及 将它们维持在集中式的繁殖和分销设施中。这 第二个目标是继续已经建立的协作研究 克隆这些疾病的基因，研究细胞和分子 这些疾病的生物学，并开发用于治疗干预的方法。 第三个方面是提供物理和人员资源 在该项目的支持下，用于制定和进行治疗试验 由独立研究调查员发起，无论是学术还是 工业组织。每个这样的协作研究都经过同行评审， 另外，作为合作研究者研究方案的一部分。 五种狗菌株，每种菌株都会传播一个不同的基因以表征良好 遗传性视网膜变性（杆状发育不良1型RCDL，进展 杆孔变性PRCD，早期视网膜变性ERD，锥变性 CD和新近可用的RPE65突变犬应变），合适 未受影响的对照犬将被育种和维护。这些后代 狗将直接或直接分发给研究调查员 收集，加工和分布要求的组织。利用 这些突变体将通过调查人员的要求来促进这些突变体。 将向调查人员提供开发和实施的协助 这些突变体最佳利用的特定方案。 具体协作研究包括：识别，克隆和 表征CD，ERD，PRCD和RCDL中的基因； CD，ERD和PRCD；决定 并比较程序性细胞死亡基因在CD，ERD，PRCD和RCDL中的作用； 定义Docosaehexanoic acrid antryce＆ PRCD中的代谢并确定负责这些的候选基因 缺陷；进一步开发遗传性视网膜变性的疗法 包括载体介导的基因转移到犬类感光体中； 感光细胞和视网膜色素上皮细胞移植到犬 视网膜并应用视觉旋转硅芯片视网膜植入物。