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.

说明：（申请人的摘要）本申请的目的是使 可供研究界使用的某些犬种， 遗传性视网膜变性，以促进研究， 这些疾病的病因和治疗方法。这个资源项目， 过去20年来，由主要研究者持续管理， 三大方面。第一是作为生产中心， 分发，主要是向其他独立研究调查员分发， 影响人类的遗传性视网膜变性的突变犬模型。的 需要这些动物在研究中得到解决，因为这是重要的 将它们集中饲养和分配。的 第二个目标是继续进行已经建立的合作研究， 克隆这些疾病的基因，研究这些疾病的细胞和分子生物学特征， 研究这些疾病的生物学，并开发治疗干预的方法。 第三方面是提供物质和人力资源 在该项目的支持下， 由独立的研究人员发起，无论是从学术或 工业组织。每一项这样的合作研究都经过同行评审， 作为合作研究者研究协议的一部分。 五个品种的狗，每一个传递不同的基因， 遗传性视网膜变性（视杆-视锥发育不良1型RCDL，进行性 视杆-视锥变性，早期视网膜变性，视锥变性 cd和新获得的RPE 65突变体狗品系），连同适当的 未受影响的对照犬将进行繁殖和饲养。它们的后代 狗将被分发给研究人员，直接或通过 收集、处理和分发所需组织。利用 这些变种人将通过向调查人员征求要求而得到晋升。 将协助调查人员制定和实施 最佳利用这些突变体的具体方案。 具体的合作研究包括：识别，克隆， 表征cd、erd、prcd和rcdl中的基因; cd、erd和prcd;确定 比较程序性细胞死亡基因在CD、ERD、PRCD和RCDL中的作用; 确定二十二碳六烯酸转运异常的原因， 代谢在PRCD和确定候选基因负责这些 进一步开发遗传性视网膜变性的治疗方法 包括载体介导的基因转移到犬光感受器中; 视网膜色素上皮细胞和光感受器细胞移植的实验研究 视网膜;以及视觉修复硅芯片视网膜植入物的应用。