Eye Mutant Resource

眼睛突变体资源

• 批准号: 10220980
• 负责人: BO CHANG
• 金额: $ 52.01万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220980
• 关键词: Advanced Development; Age related macular degeneration; Alleles; Anatomy; Biological Models; Blindness; Cell physiology; Cells; Clinical; Collection; Communities; Complication; Cryopreservation; Defect; Development; Diabetic Retinopathy; Disease; Ensure; Environment; Eye; Eye diseases; Future; Genetic; Genotype; Glaucoma; Growth; Heritability; Human; Immunohistochemistry; Inbred Strain; Inherited; Innovative Therapy; Laboratories; Libraries; Light; Literature; Maps; Methods; Modeling; Molecular; Muller' s cell; Mus; Mutant Strains Mice; Mutation; Nature; Paper; Pathologic; Pathology; Pathway interactions; Phenotype; Physiology; Play; Prevalence; Publications; Publishing; Reproducibility; Research; Research Personnel; Resources; Retina; Retinal Diseases; Retinopathy of Prematurity; Role; Services; Site; System; Systems Analysis; Technical Expertise; The Jackson Laboratory; Transmission Electron Microscopy; Variant; Vascularization; Vision; Vision research; Visual impairment; Work; base; behavior test; chromosomal location; clinically relevant; disease natural history; disease phenotype; exome; genome-wide; geographic atrophy; human disease; human model; image guided; meetings; mouse model; mutant; neovascular; neovascularization; novel; novel therapeutics; preservation; programs; public health relevance; regenerative therapy; repository; response; screening program; success; therapeutic evaluation; web site

PROJECT SUMMARY/ABSTRACT Throughout the literature there are a myriad of examples of mouse models playing a central role in furthering our understanding of human diseases. Therefore, the need for mouse models, with their well- developed genetics and similarity to human physiology and anatomy, is clear. Mice carrying mutations that alter developmental pathways or cellular function provide model systems for analyzing defects in comparable human disorders and for serving as a resource to test therapeutic strategies. Mutant mice also provide reproducible, experimental systems for elucidating pathways of normal development and function, and of pathological responses. The primary objective of the Eye Mutant Resource (EMR) at The Jackson Laboratory is to discover, characterize and preserve mice with ocular disorders and to make them available to the vision research community. The EMR has distributed 35 mouse models of ocular disease to the vision research community and has also contributed to the development of many new therapies. For example, by using Gnat1rd17Gnat2cpfl3 double mutant mice from the EMR, researchers restored some vision in mice with a congenital blindness by changing Müller glia, which are supportive cells in the retina, into light-sensing cells. The findings may help advance the development of regenerative therapies for blinding eye diseases. In this application, we aim to screen for additional ocular mutants and characterize, at the clinical and molecular level, subretinal neovascularization and glaucoma models previously identified in our screening program. Aberrant neovascular growth is a serious complication in many eye diseases, such as retinopathy of prematurity, diabetic retinopathy, wet age-related macular degeneration (AMD), neovascular-associated geographic atrophy, and certain inherited retinopathies, causing significant vision impairment and blindness. Glaucoma is expected to reach a global prevalence of 111.8 million by 2040. These models may identify novel molecules/pathways involved in the respective diseases and provide a resource for further in-depth research and a platform to test therapeutic strategies. We will also continue our distribution of ocular mouse models and work toward enhancing the EMR and making it more self-sufficient. The Jackson Laboratory (JAX), with the world's largest collection of mouse mutant stocks and genetically diverse inbred strains, is an ideal environment to discover genetically determined ocular variations and disorders. It is also an ideal place to site the repository from which ocular models can be distributed to investigators to support and promote vision research world-wide. The technical expertise, economies of scale, and networks for resource distribution at JAX enhance the quality and the likelihood of continued success of the Eye Mutant Resource (EMR).

项目摘要/摘要 在整个文献中，有无数的鼠标模型在 进一步了解我们对人类疾病的理解。因此，对鼠标模型的需求以及他们的良好 显而易见的是，发展的遗传学和与人类生理和解剖结构的相似性。携带突变的小鼠 更改发育途径或蜂窝功能提供模型系统，用于分析可比的缺陷 人类疾病并作为测试治疗策略的资源。突变小鼠也提供 可再现的，可阐明正常发育和功能途径的实验系统，以及 病理反应。杰克逊实验室的眼突变资源（EMR）的主要目标 是发现，表征和保存具有眼部疾病的老鼠，并使它们能够获得视力 研究社区。 EMR已将35个小鼠的眼病模型分配给视力研究 社区，也为许多新疗法的发展做出了贡献。例如，通过使用 来自EMR的GNAT1RD1RD17GNAT2CPFL3双重突变小鼠，研究人员用A恢复了小鼠的某些视力 先天性失明通过改变视网膜中受支持的细胞的MüllerGlia变成光感应细胞。 这些发现可能有助于促进盲目疾病的再生疗法的发展。 在此应用中，我们旨在筛选其他眼突变体，并在临床上进行特征 先前在我们的筛选中鉴定的分子水平，视网膜下新血管形成和青光眼模型 程序。在许多眼科疾病中，异常的新生血管生长是严重的并发症，例如 早产，糖尿病性视网膜病，与年龄相关的黄斑变性（AMD），新血管相关 地理萎缩和某些遗传性视网膜病，造成了严重的视力障碍和失明。 预计到2040年，青光眼预计将达到1.118亿的全球患病率。 相对疾病涉及的分子/途径，并为进一步的深入研究提供了资源 以及测试治疗策略的平台。我们还将继续分布眼小鼠模型和 致力于增强EMR并使其更加自给自足。杰克逊实验室（JAX）， 世界上最大的小鼠突变体库存和遗传学杂种菌株的收藏是理想的 发现普遍确定的眼部变化和疾病的环境。这也是一个理想的地点 可以将眼模模型分发给研究人员以支持和促进视觉的存储库 全球研究。用于资源分配的技术专长，规模经济和网络 JAX增强了眼突变资源（EMR）持续成功的质量和可能性。