MODELS OF HUMAN HEREDITARY EYE DISEASES

人类遗传性眼病模型

• 批准号: 2161693
• 负责人: JOHN R HECKENLIVELY
• 金额: $ 24.83万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2161693
• 关键词: animal breeding; autosomal recessive trait; chromosome disorders; congenital eye disorder; disease /disorder model; electrooculography; electroretinography; genetic disorder; genetic mapping; genetic strain; inbreeding; laboratory mouse; linkage mapping; macular degeneration; mutant; retina degeneration

There is a great need for a systematic approach to identify and describe genetically-determined eye disorders in mice. First, there is significant value that experimental animal models of human eye conditions can bring to human ocular research. Our preliminary screening of mouse colonies, strains and mutant stocks at the Jackson Laboratory, using modified clinical techniques including electroretinograms, revealed a large number of mouse ocular abnormalities heretofore not known or well characterized, which have special relevance to human disorders. These include slow and fast retinal degenerations, corneal dystrophy and dysgenesis, dominant and recessive cataracts, persistent hyperplastic primary vitreous, Peter's anomaly, posterior staphyloma, optic atrophy, micro-ophthalmia, and possibly macular degeneration (degeneration with drusen). Second, there is an exceptionally high genetic homology between human and mouse genomes permitting accurate prediction of mapping locations of human ocular diseases from our knowledge of mapping the homologousloci in mouse. Five loci have been mapped for the first time in this study with mapping experiments underway with several others. Since only a portion of the 1500 or so Jackson stocks have been evaluated, and since new mutations regularly are found among the large animal colonies, it is expected that many more important ocular models will come to light. Furthermore, upon initial characterization of the clinical and genetic features of these mutations, there is a mechanism in place to maintain and distribute animals to the research community. The methodology calls for a true partnership between a clinician/ophthalmologist and a mouse geneticist/mapping expert. The protocol includes the continual screening of large numbers of strains and mutants by biomicroscopy, indirect ophthalmoscopy and ERG. Along with clinical characterization of disorders, studies of genetic etiology and mapping are being done. The uniqueness of each disorder, thus will be confirmed by breeding experiments and linkage analysis. Publications of findings will be made so that disorders are known and made available immediately to other researchers. Further in-depth studies will be done in our laboratories specifically on retinal disorders and in the laboratories of other interested collaborators.

非常需要系统的方法来识别和描述 小鼠遗传确定的眼部疾病。 首先，有重要的 价值人类眼睛条件的实验动物模型可以带来 人眼研究。 我们对小鼠菌落的初步筛查， 杰克逊实验室的应变和突变库存，使用改良 临床技术在内，包括电子图，显示了大量 迄今未知或表征的小鼠眼异常 与人类疾病具有特殊相关性。 这些包括慢和 快速视网膜变性，角膜营养不良和失去障碍，显性和 隐性白内障，持续的增生原代玻璃体，彼得 异常，后纹状体瘤，视神经萎缩，微感觉和 可能是黄斑变性（与drusen变性）。 第二，有 人与小鼠基因组之间异常高的遗传同源性 允许准确预测人眼的映射位置 从我们对小鼠中同源物构图的知识中得出的疾病。 五 基因座在本研究中首次被映射到映射 实验正在与其他几个人进行。 由于只有1500的一部分 大约已经评估了杰克逊股票，并且由于定期新突变 被发现在大型动物殖民地中，预计会有更多 重要的眼模型将曝光。 此外，初始 这些突变的临床和遗传特征的表征， 有一种机制来维持和分配动物到 研究社区。 该方法要求在 临床医生/眼科医生和小鼠遗传学家/地图专家。 这 协议包括持续筛选大量菌株和 通过生物显微镜，间接眼镜检查和ERG进行突变体。 以及 疾病的临床表征，遗传病因的研究和 映射正在完成。 因此，每个疾病的独特性将是 通过育种实验和连锁分析确认。 发现发现的出版物将成为已知和疾病的出版物 立即向其他研究人员提供。 进一步的深入研究将 在我们的实验室中专门完成视网膜疾病和 其他感兴趣的合作者的实验室。