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Understanding the relevance of hemoglobin in RPE

了解血红蛋白与 RPE 的相关性

基本信息

批准号：
9916765
负责人：
Pamela M Martin
金额：
$ 19.22万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9916765
关键词：
Aging Animal Model Anti-Inflammatory Agents Antioxidants Back Basic Science Biological Models Blindness Cell Maintenance Cell Survival Cell physiology Cells Clinical Communities Data Development Diabetes Mellitus Disease Ensure Epithelial Physiology Erythrocytes Erythroid Erythroid Cells Failure Functional disorder Funding Mechanisms Gene Expression Gene Expression Regulation Generations Genes Genetic Globin Goals Health Hemoglobin Homeostasis Human Hypoxemia In Vitro Inflammation International Ischemia Knockout Mice Knowledge Laboratories Maintenance Metabolism Modeling Molecular Morphology Mosaicism Mus Mutate Neurons Outcome Oxidative Stress Oxygen Pathologic Pattern Penetrance Pharmacology Photoreceptors Production Property Proteins Publishing Research Research Project Grants Retina Retinal Degeneration Retinal Diseases Risk Rodent Model Role Sickle Cell Sickle Cell Anemia Structure of retinal pigment epithelium Study models Time Tissues Vision cell type conditional knockout design gene function high reward high risk humanized mouse immunoregulation in vivo in vivo Model innovation knockout gene mouse model novel offspring preservation success tool virtual

项目摘要

This study will generate a humanized RPE-specific globin gene knockout mouse to elucidate the function of hemoglobin in retinal pigment epithelial (RPE) cells. RPE cells serve many functions essential to the maintenance of outer retinal health and overall visual function. Newly discovered among these, is the production of hemoglobin, a phenomenon once thought to be reserved exclusively for cells of erythroid lineage. We hypothesize that RPE-hemoglobin is important for the maintenance of RPE and retinal morphology and visual function in addition to maintenance of oxygen homeostasis in outer retina. Our prior studies have confirmed the production of hemoglobin by RPE, however the functional significance of RPE-generated hemoglobin has not been demonstrated. There is no live animal model available that allows for the study of non-erythroid (RPE)-generated hemoglobin independent of that generated by erythroid cells. The proposed study seeks to develop one. Specifically, we will generate a humanized conditional globin gene knockout mouse, a model that expresses human hemoglobin in all hemoglobin-expressing cell types except RPE. The consequences of the absence of hemoglobin in RPE in this model will provide invaluable information regarding the function of RPE-hemoglobin under normal conditions. Additionally, the novel animal model to be generated, a humanized conditional hemoglobin knockout mouse, will be made readily available to the broader research community as a tool to study the cell-type specific significance of hemoglobin.

本研究将产生人源化rpe特异性珠蛋白基因敲除小鼠来阐明其功能