CORE--ANIMAL MODELS

核心--动物模型

• 批准号: 6967762
• 负责人: Brian P Sorrentino
• 金额: $ 45.09万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967762
• 关键词: Macaca mulatta; animal breeding; animal care; animal colony; biological models; biomedical facility; disease /disorder model; gene therapy; genetically modified animals; genotype; hematopoietic tissue transplantation; immunosuppression; laboratory mouse; sickle cell anemia; veterinary science

The Animal Models Core provides critical support for the animal research proposed in all 4 projects. Support is provided for the maintenance of the transgenic mouse colonies used in the Program Project Grant. These colonies provide necessary models for the study of erythropoiesis, hemoglobin switching, and for vector-induced insertional mutagenesis. This Core provides funds for cage costs, and a research technician for genotype and breeding services. This Core also provides the expertise and resources necessary for the rhesus macaque autologous transplantation model used in projects 3 and 4. This model is essential for the further development of safe and effective gene therapy approaches to sickle cell disease. For example, the rhesus macaque model provides an accurate assessment of the efficiency by which lentiviral vectors can transduce human hematopoietic stem cells (HSCs), and whether expression of the transferred globin gene will occur at potentially therapeutic levels. Primates are also necessary to develop in vivo HSC selection strategies, given our prior experience that mouse models alone are insufficient for these studies. The Core provides expert technical services for the entire transplantation procedure, the supplies necessary to accomplish the transplant and the support the animals will require through the period of immunosuppression. We have developed a state of the art primate facility, with particular emphasis on the humane care and psychological well being of the animals, and have the necessary expertise to perform these experiments at a level commensurate with human stem cell transplantation.

动物模型核心为在所有4个项目中提出的动物研究提供了重要的支持。为维护程序赠款中使用的转基因鼠标菌落提供了支持。这些菌落为促红细胞生成，血红蛋白切换和载体诱导的插入诱变提供了必要的模型。该核心为笼子成本提供资金，以及用于基因型和繁殖的研究技术人员 服务。该核心还提供了项目3和4中使用的恒河猴自体移植模型所需的专业知识和资源。该模型对于进一步开发安全有效的基因治疗方法至关重要。例如，恒河猕猴模型提供了对慢病毒载体可以转导人造血干细胞（HSC）的效率的准确评估，以及转移的球蛋白基因的表达是否会在潜在的治疗水平上发生。鉴于我们的先前经验，灵长类动物也必须用于制定体内HSC选择策略 仅小鼠模型不足以用于这些研究。核心为整个移植程序提供了专家技术服务，完成移植所需的供应以及在免疫抑制期间所需的支持。我们已经开发了一种艺术的灵长类动物设施，特别着重于动物的人道护理和心理健康，并具有与人类干细胞移植相称的水平进行这些实验的必要专业知识。