Analysis of genes involved in the pathogenesis of the arthritis using animal disease models..

使用动物疾病模型分析涉及关节炎发病机制的基因。

• 批准号: 17500284
• 负责人: SAIJO Shinobu
• 金额: $ 2.43万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17500284/
• 关键词: Animal disease models; cytokine; Rheumatoid arthritis; Inflammation; Dendritic cells; C-type lectin; Autoimmune; Innate immunity; マウス; 自己免疫疾患; ノックアウトマウス; トランスジェニックマウス; 発生工学; 網羅的解析

Recent development of transgenic techniques has made it possible to directly analyze the function of a particular gene in a living animal. These techniques have also made it possible to produce various animal disease models as well as tools to analyze them. In this project, we used two arthritis models that we originally developed. One is HTLV-I Tg mouse and the other one is IL-1Ra KO mouse. To identify genes involving in the pathogenesis of arthritis, we analyzed the gene expression profiles of these animal models by using high-density oligonucleotide arrays. We extracted 554 genes whose expression significantly changed in both models, assuming that pathogenically important genes at the effector phase would change in both models. Interestingly, we found that C-type lectin was up-regulated in the mice. To examine the roles of these genes, we produced three of the C-type lectin KO mice including Dectin-1 and DCIR. In vivo, b-glucan induced cytokine production from wild-type mice and macrophages was abolished in Dectin-1 KO mice. In vivo, Dectin-1 mice was susceptible against fungal infection.

转基因技术的最新发展使得直接分析活体动物中特定基因的功能成为可能。这些技术也使得制作各种动物疾病模型以及分析它们的工具成为可能。在这个项目中，我们使用了我们最初开发的两个关节炎模型。一个是HTLV-I Tg小鼠，另一个是IL-1Ra KO小鼠。为了确定参与关节炎发病机制的基因，我们利用高密度寡核苷酸阵列分析了这些动物模型的基因表达谱。我们提取了554个基因，这些基因的表达在两种模型中都发生了显著变化，假设在效应期的重要致病基因在两种模型中都会发生变化。有趣的是，我们发现c型凝集素在小鼠中上调。为了研究这些基因的作用，我们生产了三种c型凝集素KO小鼠，包括Dectin-1和DCIR。在体内，b-葡聚糖诱导的野生型小鼠和巨噬细胞产生的细胞因子在Dectin-1 KO小鼠中被消除。在体内，Dectin-1小鼠对真菌感染敏感。

项目成果

The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors

• DOI: 10.1038/ni1466
• 发表时间: 2007-06-01
• 期刊: NATURE IMMUNOLOGY
• 影响因子: 30.5
• 作者: Hara, Hiromitsu;Ishihara, Chitose;Saito, Takashi
• 通讯作者: Saito, Takashi

IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia

• DOI: 10.1038/nm1710
• 发表时间: 2008-03-01
• 期刊: NATURE MEDICINE
• 影响因子: 82.9
• 作者: Aujla, Shean J.;Chan, Yvonne R.;Kolls, Jay K.
• 通讯作者: Kolls, Jay K.

A C-type lectin that involved in host defense against fungi plays an important role in the development of arthritis

参与宿主防御真菌的 C 型凝集素在关节炎的发展中发挥重要作用

• 发表时间: 2007
• 作者: Matsuki;I.;Isoda;K.;Horai;R.;Nakajima;A.;Aizawa Y.;Suzuki;K.;Ohsuzu;F.;Iwakura;Y.;岩倉洋一郎;岩倉 洋一郎;角田茂;Yoichiro Iwakura;Yoichiro Iwakura;Yoichiro Iwakura;Soo-hyun Chung;Harumichi Ishigame;Harumichi Ishigame;Shinobu Saijo;Noriyuki Fujikado;Yoichiro Iwakura;Yoichiro Iwakura;Yoichiro Iwakura;Yoichiro Iwakura;Harumichi Ishigame;Noriyuki Fujikado;Shinobu Saijo
• 通讯作者: Shinobu Saijo

マイクロアレイと疾患モデル動物を用いた新規関節炎関連遺伝子の解析

使用微阵列和疾病模型动物分析新型关节炎相关基因

• 发表时间: 2005
• 作者: Matsuki;I.;Isoda;K.;Horai;R.;Nakajima;A.;Aizawa Y.;Suzuki;K.;Ohsuzu;F.;Iwakura;Y.;岩倉洋一郎;岩倉 洋一郎;角田茂;Yoichiro Iwakura;Yoichiro Iwakura;Yoichiro Iwakura;Soo-hyun Chung;Harumichi Ishigame;Harumichi Ishigame;Shinobu Saijo;Noriyuki Fujikado;Yoichiro Iwakura;Yoichiro Iwakura;Yoichiro Iwakura;Yoichiro Iwakura;Harumichi Ishigame;Noriyuki Fujikado;Shinobu Saijo;西城忍;石亀晴道;藤門範行;Noriyuki Fujikado;西城忍;角田茂;Yoichiro Iwakura;Soo-hyun Chung;Harumichi Ishigame;Harumichi Ishigame;Noriyuki Fukikado;Yoichiro Iwakura;Yoichiro Iwakura;Yoichiro Iwakura;Harumichi Ishigame;Harumchi Ishigame;Shinobu Saijo;Noriyuki Fujikado;Yoichiro Iwakura;Yoichiro Iwakura;Noriyuki Fujikado;Shinobu Saijo;石亀 晴道;西城 忍;角田茂;Shinobu Saijo;Noriyuki Fujikado;Dai Chida;Harumichi Ishigame;Noriyuki Fujikado;Shinobu Saijo;Mari Shibukawa;疇地里衣;千田大;千田大;石亀晴道;西城忍;藤門範行;関景輔;渋川茉莉;西城忍;角田茂;Shinobu Saijo;Noriyuki Fujikado;Dai Chida;Shinobu Saijo;西城忍;Noriyuki Fujikado;関景輔;橋本興人;千田大;西城忍;石亀晴道;藤門範行;西城忍;藤門範行;松木大造;西城忍
• 通讯作者: 西城忍

Identification of dendritic cell immunoreceptor as a novel arthritis-related gene by transcriptome analysis of rheumatoid

通过类风湿转录组分析鉴定树突状细胞免疫受体作为一种新型关节炎相关基因

• 发表时间: 2007
• 作者: Ishigame;H.;Nakajima;A.;Saijo;S.;Komiyama;Y.;Nambu;A.;Matsuki;T.;Nakae;S.;Horai;R.;Kakuta;S.;Iwakura;Y.;Soo-hyun Chung;Shinobu Saijo;Noriyuki Fujikado;Noriyuki Fujikado;Shinobu Saijo;西城忍;藤門範行;Noriyuki Fujikado;西城忍;Soo-hyun Chung;Shinobu Saijo;Noriyuki Fujikado
• 通讯作者: Noriyuki Fujikado