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CD73 FUNCTION DURING LYMPHOCYTE DEVELOPMENT

CD73 在淋巴细胞发育过程中的功能

基本信息

批准号：
2376900
负责人：
REGINA RESTA
金额：
$ 9.26万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-04-01 至 1998-01-01
项目状态：
已结题

项目摘要

Research Plans Ecto-5'-nucleotidase (5'-NT, CD73) is a purine salvage enzyme expressed on the surface of normal and malignant human lymphocytes. 5'-NT has signal transducing capabilities as demonstrated by the ability of 5'-NT antibodies to cause human lymphocyte proliferation. Since high expression of 5'-NT is associated with a poor prognosis in acute lymphoblastic leukemia, it is possible that this molecule transmits signals that promote the uncontrolled proliferation of these cells. 5'-NT expression appears to be highly regulated during lymphocyte development, increasing with maturation of both T and B cells. The goals of the proposed research are to determine the importance of regulated expression of 5'-NT in lymphocyte differentiation and will be examined by inappropriately overexpressing 5'-NT in early T B cells and by ablating expression in mature cells. 5'-NT will be overexpressed in either immature murine thymocytes or B cells by expressing human 5'-NT in transgenic mice under the control of the lck promoter or IgH enhancer, respectively. 5'-NT will be deleted in mature T and B cells by making knockout mice. The effect of such inappropriate expression on the histology of the thymus, spleen, bone marrow and lymph nodes in the mature mouse, and on the phenotype of T and B cells in these lymphoid organs, will be examined. The ontogeny of T and B cell development in the fetal thymus, spleen, and liver, and the function of mature T and B cells will be examined. Mice will be observed for the development of lymphoid tumors, which will be characterized if they occur. The proposed work will not only reveal new insights into the importance of regulated expression of 5'-NT during lymphocyte differentiation, but will also allow the applicant to develop skills in transgenic technology and contribute toward her development as an independent investigator.

研究计划 Ecto-5'-核苷酸酶（5'-NT，CD73）是一种嘌呤回收物正常和恶性人类淋巴细胞表面表达的酶。 5'-NT 具有信号转导能力，如 5'-NT 抗体可引起人淋巴细胞增殖。自从高 5'-NT 的表达与急性期不良预后相关淋巴细胞白血病，该分子可能传递信号促进这些细胞不受控制的增殖。 5'-NT 表达似乎在淋巴细胞发育过程中受到高度调节，随着 T 细胞和 B 细胞的成熟而增加。的目标拟议的研究是为了确定调节表达的重要性 5'-NT 在淋巴细胞分化中的作用，将通过以下方法进行检查在早期 T B 细胞中不恰当地过度表达 5'-NT，并通过消除在成熟细胞中表达。 5'-NT 将在任一未成熟细胞中过度表达通过在转基因小鼠中表达人 5'-NT 来产生小鼠胸腺细胞或 B 细胞分别受lck启动子或IgH增强子的控制。 5'-NT 通过制作基因敲除小鼠，成熟的 T 细胞和 B 细胞将被删除。这这种不恰当的表达对胸腺组织学的影响，成熟小鼠的脾脏、骨髓和淋巴结，以及将检查这些淋巴器官中 T 细胞和 B 细胞的表型。这胎儿胸腺、脾脏和 T 细胞和 B 细胞发育的个体发育肝脏，并检查成熟 T 细胞和 B 细胞的功能。小鼠将观察淋巴肿瘤的发展，这将是描述它们是否发生。拟议的工作不仅会揭示新的深入了解 5'-NT 调控表达的重要性淋巴细胞分化，但也将使申请人能够发展转基因技术技能，并为她作为一个人的发展做出贡献独立调查员。