MODELS OF HEREDITARY RETINAL DEGENERATION

遗传性视网膜变性模型

• 批准号: 2838284
• 负责人: GREGORY M ACLAND
• 金额: $ 49.37万
• 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 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2838284
• 关键词: animal breeding; animal colony; apoptosis; cell transplantation; cooperative study; disease /disorder model; dogs; gene mutation; gene therapy; genetic models; genetic strain; implant; inborn biological transport disorder; model design /development; molecular cloning; nonhuman therapy evaluation; retina degeneration; retinal pigment epithelium; silicon; transfection; visual photoreceptor

The application proposes continuation of a resource project that has been continuously managed by the principal investigators for over 16 years. The project purpose has 2 parts. The first is to serve as a central research resource for production and distribution, to other independent research investigators, of 4 canine mutant models of the hereditary retinal degenerations affecting humans. The need for these canine mutants 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. Each such collaborative study is peer reviewed, separately, as part of the collaborative investigators' research protocols. Four strains of dogs, each transmitting a different gene for well characterized hereditary retinal degenerations (rod-cone dysplasia type 1 rcd1, progressive rod-cone degeneration prcd, early retinal degeneration erd, cone degeneration cd), 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 mutations for cd, erd and prcd; determine and compare the role of programmed cell death genes in cd,erd, prcd, and rcd1; define the cause of abnormalities in docosahexanoic 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 retinal implant.

该申请提出了继续的资源项目的延续 由主要研究人员不断管理16年以上。这 项目目的有2个部分。首先是作为中心研究 生产和分销资源，其他独立研究 研究人员的4个犬类视网膜犬突变模型 影响人类的退化。需要这些犬突变体 研究已经解决，将它们维持在 集中化和分销设施。第二个目标是 继续建立协作研究以克隆基因 这些疾病，研究了这些疾病的细胞和分子生物学 疾病，并开发治疗干预的方法。 每个这样 协作研究将分别作为同行评审 协作研究人员的研究方案。 四种狗菌株，每种菌株都会传递一个不同的基因以供井 表征遗传性视网膜变性（杆状发育不良1型 RCD1，进行性杆锥变性PRCD，早期视网膜变性 ERD，锥变性CD），以及适当的非影响对照 狗，将繁殖和维护。这些狗的后代将是 直接或通过收集分发给研究调查员 请求组织的加工和分布。这些利用 突变体将通过调查人员的要求来促进突变体。 将向开发的调查人员提供援助 实施特定协议以最佳利用 突变体。 具体协作研究包括：识别，克隆和 表征CD，ERD和PRCD的基因突变；确定和 比较程序性细胞死亡基因在CD，ERD，PRCD和RCD1中的作用； 定义docosahexanoic acrid转运和 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的疗法 退化包括载体介导的基因转移到犬 感受器；感受器和视网膜色素上皮细胞 移植到犬类视网膜中；和视觉旋转的应用 硅视网膜植入物。