Erstellen einer Knockout Maus als Modell für die X-gekoppelte lymphoproliferative Erkrankung und Analyse des SH2D1A Gens auf eine mögliche Tumorsuppressorfunktion an Non-Hodkin-Burkitt Tumor Zellinien

创建敲除小鼠作为 X 连锁淋巴增殖性疾病模型，并分析 SH2D1A 基因对非霍德金-伯基特肿瘤细胞系可能的肿瘤抑制功能

• 批准号: 5239331
• 负责人: Dr. Oliver Brandau
• 金额: --
• 依托单位: Max-Planck-Institut für Biochemie (MPIB)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2001-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5239331?language=en
• 关键词: Erstellen; einer; Knockout; Maus; als

The SH2D1A gene is mutated in about 70 % of X-linked lymphoproliferative disease (XLP) patients and also in Epstein-Barr Virus (EBV) negative patients with early onset non-Hodgkin Burkitt lymphoma (NHBL). SH2D1A codes for an SH2-domain protein, which inhibits the activation of a signalling cascade regulating proliferation and differentiation of B- and T-cells. The occurrence of SH2D1A mutations in patients with early onset NHBL, independent of EBV infection, suggests a tumor suppressor function for the SH2D1A gene. I will create an SH2D1A-null mouse to serve as a model for XLP and to study the downstream signalling from SH2D1A. To investigate the functional properties of this gene in terms of tumor propagation a NHBL cell line from an XLP patient will be established and transfected with SH2D1A. Overexpression of proteins inhibited by SH2D1A in NHBL lines BJAB, CA46 and MC116 is proposed, to analyse if these proteins are involved in the high malignancy of NHBLs with a duplication of chromosome 1q23-25.

约70%的x连锁淋巴细胞增生性疾病（XLP）患者和eb病毒（EBV）阴性的早期非霍奇金伯基特淋巴瘤（NHBL）患者中存在SH2D1A基因突变。SH2D1A编码sh2结构域蛋白，该蛋白抑制调节B细胞和t细胞增殖和分化的信号级联的激活。早发性NHBL患者中SH2D1A突变的发生，独立于EBV感染，提示SH2D1A基因具有肿瘤抑制功能。我将创建一个SH2D1A缺失的小鼠作为XLP的模型，并研究来自SH2D1A的下游信号。为了研究该基因在肿瘤增殖方面的功能特性，将建立XLP患者的NHBL细胞系并转染SH2D1A。我们提出在NHBL细胞系BJAB、CA46和MC116中过量表达SH2D1A抑制的蛋白，以分析这些蛋白是否与染色体1q23-25重复的NHBL高恶性肿瘤有关。