CORE--ANIMAL MODELS

动物模型核心为所有4个项目中提出的动物研究提供关键支持。为项目赠款中使用的转基因小鼠群体的维护提供支持。这些菌落为研究红细胞生成、血红蛋白转换和载体诱导的插入突变提供了必要的模型。这个核心为笼子成本提供资金，并为基因分型和育种提供研究技术员 服务。该核心还为项目3和项目4中使用的恒河猴自体移植模型提供必要的专业知识和资源。该模型对于进一步开发安全有效的镰状细胞疾病基因治疗方法至关重要。例如，恒河猴模型可以准确评估慢病毒载体转导人类造血干细胞(HSCs)的效率，以及转移的珠蛋白基因是否会在潜在的治疗水平上表达。考虑到我们以前的经验，灵长类动物也是发展体内HSC选择策略所必需的 仅靠老鼠模型是不足以进行这些研究的。该中心为整个移植程序提供专家技术服务，提供完成移植所需的用品，并在免疫抑制期间为动物提供所需的支持。我们开发了最先进的灵长类设施，特别强调动物的人文关怀和心理健康，并拥有必要的专业知识，在与人类干细胞移植相称的水平上进行这些实验。

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.