CD73 FUNCTION DURING LYMPHOCYTE DEVELOPMENT

CD73 在淋巴细胞发育过程中的功能

• 批准号: 2102596
• 负责人: REGINA RESTA
• 金额: $ 8.01万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2102596
• 关键词: 5' nucleotidase; animal genetic material tag; enzyme activity; enzyme induction /repression; gastrointestinal system; gene deletion mutation; gene expression; genetic enhancer element; genetic promoter element; genetically modified animals; growth /development; laboratory mouse; leukocyte activation /transformation; leukopoiesis; lymph nodes; lymphocyte; lymphoma; molecular cloning; neoplasm /cancer genetics; recombinant DNA; reproductive system; spleen; thymus; transfection /expression vector; vertebrate embryology

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.

研究计划胞外-5‘-核苷酸酶(5’-NT，CD73)是一种嘌呤残留物 正常和恶性人淋巴细胞表面均有酶的表达。 5‘-NT具有信号转导能力，这一点体现在 5‘-NT抗体可引起人淋巴细胞增殖。从高到高 5‘-NT的表达与急性白血病预后不良相关 淋巴细胞性白血病，这种分子有可能传递信号 促进了这些细胞的不受控制的增殖。5‘-NT 在淋巴细胞发育过程中，表达似乎受到高度调控， 随着T细胞和B细胞的成熟而增加。世界银行的目标是 拟议的研究是为了确定受调控表达的重要性 5‘-NT在淋巴细胞分化中的作用 早期T-B细胞中5‘-NT的不适当过度表达和消融 在成熟细胞中表达。5‘-NT在任何一个未成熟的组织中都会过度表达 在转基因小鼠中表达人5‘-NT的小鼠胸腺细胞或B细胞 分别在LCK启动子或IgH增强子的控制下。5‘-NT 将通过制造基因敲除小鼠在成熟的T和B细胞中被删除。这个 这种不适当的表达对胸腺组织学的影响， 成熟小鼠的脾、骨髓和淋巴结节，以及 将检查这些淋巴器官中T和B细胞的表型。这个 胎儿胸腺、脾和胸腺中T和B细胞的个体发育 肝脏，并检测成熟T细胞和B细胞的功能。老鼠 将观察淋巴样肿瘤的发展情况，这将是 如果它们发生了，就表现出了特征。拟议中的工作不仅将揭示新的 对5‘-NT调控表达的重要性的认识 淋巴细胞分化，但也将允许申请者发育 在转基因技术方面的技能，并为她作为一名 独立调查员。