TRANSFERRIN RECEPTOR AND ERYTHROPOIESIS

转铁蛋白受体和红细胞生成

• 批准号: 6043667
• 负责人: JOANNE E LEVY
• 金额: $ 10.87万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6043667
• 关键词: animal breeding; embryonic stem cell; erythropoiesis; genetically modified animals; ion transport; iron; iron disorder; transferrin receptor

The candidate is an M.D. who has completed full medical training including clinical hematology/oncology fellowship and is now intensively pursuing basic research with the ultimate goal of a career as an independent investigator. The research will be carried out in the hematology division of a major teaching hospital. The laboratory group focuses on erythroid development, and has expertise in molecular biology and transgenic technology. The research project investigates red cell differentiation and development. Iron deficiency is the leading cause of anemia world wide, with conservative estimates of over 0.5 billion people affected; however, despite this frequency its pathophysiology is incompletely understood. The project outlined focuses on the role of iron in regulating red cell differentiation and development with the goal of increasing understanding of the block to normal erythropoiesis in iron deficiency. The transferrin receptor will be genetically manipulated in murine embryonic stem cells. These cells will be injected into mouse blastocysts and bred to homozygosity to allow in vivo study of the transferrin cycle. If homozygous mice are non-viable chimeric mice will be generated using embryonic stem cells in which both copies of the transferrin receptor have been altered. Experiments are also planned utilizing the technique of in vitro erythroid differentiation of these genetically altered embryonic stem cells. Information learned will lead to increased understanding of the block to red cell production in iron deficiency, and ultimately to the development of new treatment strategies for iron deficiency and iron overload.

候选人是一名医学博士，他已经完成了全面的医学培训 包括临床血液学/肿瘤学奖学金，现在很强烈 追求基础研究，以职业生涯的最终目标 独立研究者。 该研究将在 一家大型教学医院的血液学师。 实验室 专注于红斑发展，并具有分子生物学的专业知识 和转基因技术。研究项目调查了红细胞 分化和发展。铁缺乏症是 全球贫血，保守的估计超过5亿人 做作的;然而，尽管如此，它的病理生理学是 不完全理解。 该项目概述着专注于 铁在调节红细胞分化和开发方面的铁 越来越了解铁中正常红细胞生成的块 不足。 转铁蛋白受体将在遗传上操纵 鼠类胚胎干细胞。 这些单元将注入鼠标 胚泡并繁殖到纯合性，以允许体内研究 转铁蛋白周期。如果纯合小鼠是不可生存的嵌合小鼠 使用胚胎干细胞生成 转铁蛋白受体已改变。 还计划了实验 利用这些体外红细胞分化的技术 遗传改变的胚胎干细胞。学到的信息将领导 增加对铁中红细胞产生的块的了解 不足，最终发展新的治疗策略 用于铁缺乏和铁超负荷。