The Mouse Blood Center Core

小鼠血液中心核心

• 批准号: 10192791
• 负责人: JEANNE E HENDRICKSON
• 金额: $ 41.79万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10192791
• 关键词: Adenine; Alloimmunization; Animals; Antibodies; Antibody Formation; Antigens; Back; Backcrossings; Biological Assay; Blood; Blood Component Removal; Blood Group Antigens; Blood Platelets; Blood donor; Breeding; Characteristics; Chimeric Proteins; Citrates; Coagulation Process; Collection; Dangerousness; Data; Disease; Donor Selection; Equipment; Erythrocyte Transfusion; Erythrocytes; Female; Fetus; Flow Cytometry; Gel; Genetic Drift; Glucose; Glycoproteins; Goals; Hemolysis; Hen Egg Lysozyme; Hospitals; Hour; Human; IgG1; IgG3; Immune response; Immunobiology; Immunoglobulin G; Immunoglobulin M; Inflammation; Inflammatory; Iodides; Isoantibodies; Laboratories; Measures; Methods; Mind; Modeling; Mouse Strains; Mus; Newborn Infant; Ovalbumin; Phosphorus; Pregnancy; Preparation; Process; Program Research Project Grants; Public Health; Quality Control; Reaction; Reagent; Recovery; Research Personnel; Resources; Running; Sampling; Scanning; Serum; Services; Ships; Site; Sum; Temperature; Testing; Transfusion; Transgenic Animals; Transgenic Mice; Transgenic Organisms; Whole Blood; antibody detection; blood product; clinically significant; cost; cytokine; experience; genome-wide; immunohematology; innovation; male; mouse model; premature; response; screening; transfusion medicine

Project Summary Background: RBC alloimmunization is a clinically significant problem in transfusion and pregnancy settings alike. Given the number of variables involved in human studies, the projects in this PPG have taken the approach of using reductionist murine models to generate a better overall understanding of factors influencing RBC alloimmunization. This proposed Mouse Blood Center Core (Core B) will support the 4 PPG projects by providing leukoreduced, quality controlled, transgenic RBCs for transfusion. Further, this Core will serve as a central immunohematology reference Laboratory for alloantibody testing. In addition to optimizing resource utilization and efficiency, the products and services provided by this Core will allow for more direct comparison of results between sites and projects. Innovation: The mouse donor strains proposed for use in these studies, generated and characterized by PPG investigators, allow for isolation of the effects of single variable changes on alloimmunization. The HOD donors have a triple fusion protein on their RBCs, composed of hen egg lysozyme, ovalbumin, and the human Duffyb antigen. The KEL donors have the entire human KEL glycoprotein expressed in an RBC specific manner, with K1 as well as K2 donors being used in this proposal. Antibodies generated by wild type recipient mice transfused with transgenic HOD, K1, or K2 RBCs are clinically significant, resulting in premature RBC clearance, hemolytic transfusion reactions, and hemolytic disease of the fetus and newborn (HDFN). Specific Aim 1: To breed and maintain transgenic mice expressing model or human blood group antigens on their RBCs. Specific Aim 2: To collect, process, perform quality control measures, and distribute donor RBCs from these transgenic animals to all 4 PPG sites. Specific Aim 3: To serve as an immunohematology reference laboratory for antibody detection.

项目摘要 背景：红细胞同种异体免疫是输血和妊娠环境中的一个临床重要问题 一模一样。考虑到人体研究中涉及的变量数量，本PPG中的项目采用了 使用还原论小鼠模型的方法，以更好地全面了解因素 影响RBC同种免疫。该拟定小鼠血液中心核心（核心B）将支持4 PPG 通过提供用于输血的去白细胞、质量受控的转基因红细胞，此外，该核心将 作为同种抗体检测的中心免疫血液学参考实验室。除了优化 资源利用率和效率，该核心提供的产品和服务将允许更直接的 现场和项目之间的结果比较。 创新：拟定用于这些研究的小鼠供体品系，通过以下方法生成和表征： PPG研究者允许分离单个变量变化对同种免疫的影响。部门首长 供体的红细胞上有一种三重融合蛋白，由鸡蛋溶菌酶、卵清蛋白和 人Duffyb抗原。KEL供体具有在RBC中表达的整个人KEL糖蛋白 具体方式，在本提案中使用K1和K2供体。野生型产生的抗体 输注转基因HOD、K1或K2 RBC的受体小鼠具有临床意义，导致 红细胞过早清除、溶血性输血反应和胎儿和新生儿溶血性疾病 （HDFN）。 具体目标1：培育和维持表达模型或人血型的转基因小鼠 红细胞上的抗原 具体目标2：采集、处理、执行质量控制措施并分发供体RBC 从这些转基因动物到所有4个PPG位点。 具体目标3：作为抗体检测的免疫血液学参考实验室。