MOLECULAR PATHOLOGY IN DISEASES WITH DNA STRAND BREAKS AND REPAIR DEFECTS.

DNA 链断裂和修复缺陷疾病的分子病理学。

• 批准号: 13470158
• 负责人: MIZUTANI Shuki
• 金额: $ 9.22万
• 依托单位: TOKYO MEDICAL AND DENTAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470158/
• 关键词: DNA STRAND BREAKS; CD23; AID; ATM; Ku; 70; 80; クラススイッチ; がん体質; トポイソメラーゼ

Activation-Induce Cytidine Deaminase (AID) is an essential molecule for immunoglobulin class switching in B cells, and the mutation of AID is responsible for hyper-IgM syndrome type II. We identified 12 Japanese patients with hyper-IgM syndrome type II. We found R190X mutation has a dominant negative function against wild type AID.ATM is a gene involved in the pathogenesis of Ataxia Telangiectasia and plays an important role in genome surveillance system. We found germ line ATM mutation in a case with acute leukemia with MLL gene rearrangement. This mutation also had a dominant negative function against wild type ATM, suggesting an important link between ATM dysfunction and MLL gene rearrangement in childhood leukemia. We found Ku70/80 auguments TCF/beta-catenin dependent transactivation and positively regulates CD23 expression.

激活诱导型胞苷脱氨酶(AID)是B细胞免疫球蛋白类别转换所必需的分子，AID突变与高IgM综合征II型有关。我们对12例日本II型高IgM综合征患者进行了检测，发现R190X突变对野生型AID具有显性负功能。ATM基因参与了共济失调性毛细血管扩张症的发病，在基因组监测系统中发挥着重要作用。我们在1例MLL基因重排的急性白血病患者中发现了胚系ATM突变。该突变对野生型ATM也具有显性负性作用，提示ATM功能障碍与儿童白血病MLL基因重排之间存在重要联系。我们发现Ku70/80增强了TCF/β-catenin依赖的反式激活，并正向调节CD23的表达。

项目成果

Inoue, H., Nonoyama, S., et al.: "X-linked thrombocytopenia in a girl"Brit. J. Haematol.. 118. 1163-1165 (2002)

Inoue, H., Nonoyama, S., et al.：“女孩的 X 连锁血小板减少症”Brit。

Mizutani, S.: "Genetic background as a possible determinant of clinical and biological features of Epstein-Barr virus infection-a hypothetical view"Crit Rev Oncol Hematol.. 44(3). 217-255 (2002)

Mizutani, S.：“遗传背景可能是 Epstein-Barr 病毒感染的临床和生物学特征的决定因素 - 一种假设的观点”Crit Rev Oncol Hematol.. 44(3)。

Oguchi, K.., Mizutani S., et al.: "Missense mutation and defective function of ATM in a childhood acute leukemia patient with MLL gene rearrangement"Blood. in press.

Oguchi, K.., Mizutani S., et al.：“患有 MLL 基因重排的儿童急性白血病患者中 ATM 的错义突变和功能缺陷”血液。

Kimura-Oyoshi, M., Morio, T., et al.: "Preferential expansion of Vγ9-JγP/Vδ2-Jδ3 γδ T-cells in nasal γδT-ceII lymphoma and chronic active Epstein-Barr virus (EBV) infection"Am. J. Pathol.. in press.

Kimura-Oyoshi, M.、Morio, T. 等人：“鼻 γδT 细胞淋巴瘤和慢性活动性 Epstein-Barr 病毒 (EBV) 感染中 Vγ9-JγP/Vδ2-Jδ3 γδ T 细胞的优先扩增”Am J.Pathol..正在出版。

R.Tsuchida, S.Mizutani et al.: "Detection of ATM Gene Mutation in Human Glioma Cell Line M059J by a Rapid Frame-Shift/Stop Codon Assay in Yeast"Rad. Res. 158. 195-201 (2002)

R.Tsuchida、S.Mizutani 等人：“通过酵母中的快速移码/终止密码子测定检测人神经胶质瘤细胞系 M059J 中的 ATM 基因突变”Rad。