CORE--ANIMAL MODELS

动物模型将用于评估基因转移到造血干细胞中。 干细胞及其对血红蛋白合成的影响。 这项工作涉及 圣裘德儿童研究中心的研究人员之间的合作 医院和在美国国立卫生研究院的校内计划 健康 独特的免疫缺陷，转基因小鼠表达人类 细胞因子、干细胞因子、白细胞介素-3和粒细胞巨噬细胞- 集落刺激因子能够维持人类造血， 在注射原始细胞群几周后， 通过免疫学技术进行纯化。 各种载体的效率 将评估用于将基因插入这些细胞的系统。 转录单位，无论是珠蛋白基因或cDNA序列设计， 增加或降低特定转录因子的活性， 以确定成熟过程中血红蛋白合成的影响 在体内从这些原始细胞群衍生的成红细胞。 当 适当的，类似的实验将在猿基因中进行， 转移，自体骨髓移植模型，使用 具有潜在临床应用价值的实验设计。 的 将基因插入真正的再生干细胞的能力将是最好的 在这个灵长类动物移植模型中确定。

Animal models will be utilized to evaluate gene transfer into hematopoietic stem cells and its influence on hemoglobin synthesis. This work involves collaboration between investigators at St. Jude Children's Research Hospital and within the Intramural Program at the National Institutes of Health. Unique immunodeficient, transgenic mice expressing the human cytokines, stem cell factor, interleukin-3, and granulocyte macrophage- colony stimulating factor are capable of sustaining human hematopoiesis for several weeks following injection of primitive cell populations which have been purified y immunological techniques. The efficiency of various vector systems for insertion of genes into such cells will be evaluated. Transcriptional units, either a globin gene or cDNA sequences designed to increase or decrease activity of a specific transcriptional factors, will be introduced to determine the effect on hemoglobin synthesis in maturing erythroblasts derived from these primitive cell populations in vivo. When appropriate, analogous experiments will be performed in a simian gene transfer, autologous bone marrow transplantation model using an experimental design which is potentially clinically applicable. The capacity for gene insertion into true repopulating stem cells will be best determined in this primate transplantation model.