Humanized Mouse Core

人性化鼠标核心

基本信息

批准号：
9980278
负责人：
Patrizia Caposio
金额：
$ 27.01万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-15 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9980278
关键词：
AMD3100 Animal Model Applications Grants BLT mice Bone Marrow Bone Marrow Transplantation CD34 gene CD8-Positive T-Lymphocytes CSF3 gene Cells Chemicals Clinical Collaborations Cytomegalovirus Data Dendritic Cells Development EGF gene Endothelial Cells Engraftment Environment Epithelial Cells Exhibits Fetal Liver Generations Genes Goals Graft Rejection Granulocyte Colony-Stimulating Factor Growth Factor Health Sciences Hematopoiesis Hematopoietic Stem Cell Mobilization Hematopoietic Stem Cell Transplantation Hematopoietic stem cells Human Immune In Vitro Infection Injections Institutes Investigation Kidney Liver Mature B-Lymphocyte Modeling Molecular Morbidity - disease rate Mus Myelosuppression Oregon Organ Organ Transplantation Pathway interactions Patients Peptides Phenotype Population Program Research Project Grants Recombinants Reporting Research Personnel Signal Pathway Solid Stromal Cells Supervision System T cell response Testing Thymus Gland Tissues Transplant Recipients Transplantation Universities Vaccine Therapy Viral Viral Load result Virus Virus Diseases Virus Latency Virus Replication base capsule cell type cytokine experimental study fetal gene therapy human tissue humanized mouse in vivo inhibitor/antagonist macrophage mortality mouse model mutant neutralizing antibody progenitor programs seropositive small hairpin RNA stem cells

项目摘要

CORE A PROJECT SUMMARY/ABSTRACT The primary goal of this Core is to generate humanized mice that can be used to test HCMV latency and reactivation as well as hematopoiesis using HCMV mutants generated in Projects 1-5. The long-term goal of Core A is to generate huBLT mice to answer in vivo questions of HCMV latency, reactivation and hematopoiesis based on in vitro CMV models proposed in the various studies embedded in the Program Project. First, the Core will generate huBLT mice to analyze HCMV mutants generated in Projects 1-4 for their ability to establish and maintain latency and reactivate following treatment with G-CSF and AMD-3100. Once Projects 1-4 will have identified signaling pathways and/or secreted factors that are important for HCMV latency and reactivation, Core A will validate them using chemical inhibitors, neutralizing antibodies, recombinant HCMV expressing shRNAs and/or addition of cytokines/growth factors required for reactivation. Second, the Core will analyze hematopoiesis in huBLT mice infected with WT HCMV (Project 5) or viral mutants (Projects 1-4) and then will validate the results using chemical inhibitors, neutralizing antibodies, recombinant HCMV expressing shRNAs and/or addition of cytokines/growth factors required for hematopoiesis.

核心项目摘要/摘要该核心的主要目标是生成可用于测试 HCMV 潜伏期和使用项目 1-5 中产生的 HCMV 突变体进行再激活和造血。长期目标是核心 A 是生成 huBLT 小鼠，以回答 HCMV 潜伏期、重新激活和基于该计划中各种研究中提出的体外 CMV 模型的造血项目。首先，Core 将生成 huBLT 小鼠来分析项目 1-4 中生成的 HCMV 突变体的使用 G-CSF 和 AMD-3100 治疗后建立和维持潜伏期并重新激活的能力。一次项目 1-4 将确定对 HCMV 重要的信号传导途径和/或分泌因子潜伏期和重新激活，Core A 将使用化学抑制剂、中和抗体来验证它们，重组 HCMV 表达 shRNA 和/或添加重新激活所需的细胞因子/生长因子。其次，Core 将分析感染 WT HCMV（项目 5）或病毒的 huBLT 小鼠的造血功能突变体（项目 1-4），然后使用化学抑制剂、中和抗体验证结果，重组 HCMV 表达 shRNA 和/或添加造血所需的细胞因子/生长因子。