Functional and therapeutic study on inhibitory genes associated with collagen diseases

胶原蛋白疾病相关抑制基因的功能和治疗研究

• 批准号: 16390113
• 负责人: ONO Masao
• 金额: $ 9.6万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390113/
• 关键词: Autoimmune disease; SLE; Animal disease model; SAP; Signal transduction; Adaptor molecule; Autoantibody; Platelet

We have identified two mutant genes that individually cure autoimmune diseases in murine models [1,2]. Futhermore, by using two mutant strains of mice with these mutations, we attempted to identify effecter cells and molecules critically involved in the pathogenesis of autoimmune diseases in mouse models, MRL/lpr and EOD. The results provided new understandings as follows :1.The role of signal lymphocyte activation molecule (SLAM)-associated protein (SAP) in the development, of autoimmunity (Furukawa, Ono, Ishii).Concanavalin A (ConA)-induced hepatitis, which is known as a model for autoimmune hepatitis, was investigated in wild-type and SAP-deficient strains of mice. The results provided evidences that (1)SAP has a role for suppression of the development of ConA-induced hepatitis, and that (2)the suppressive effect of SAP depends upon a cellular function for hepatic injury, which is independent of Fas ligand (FasL)2.Characterization of SLAM-family receptors associated With the develop … More ment autoimmune diseases in mice (Furukawa, Ono).We constructed DNA vectors that SLAM-family receptors expressed in vivo and determined an optimal condition of the hydrostatic expression method for each of the expression construct. Effect of induced expression of each SLAM- family receptor in autoimmune mice is on investigation,3.Identification of platelet function for the development of allergic reaction in mice (Ono).We established C57BL/6J-cinn/cinn (B6^<cinn>), a congenic strain that shows a defect in platelet functions by a loss-of- function mutation on Cuppuccino gene (Cno). In B6^<cinn> mice significantly higher anaphylactic response to passive IgE challenge (IgE anaphylaxis) was observed than in wild-type mice. The difference was apparent especially in late phase of the reaction. It is indicated that platelet play a role in the recovery from IgE, anaphylaxis.4.Identifieation of platelet function for the development of experimental and spontaneous arthritis in mice (Ono).In our preliminary study, B6^<cinn> showed resistant phenotype in collagen-induced arthritis (CIA), suggesting that platelet has a suppressive role in the development of CIA. Less

我们已经鉴定了两种突变基因，它们分别在小鼠模型中治愈自身免疫性疾病[1，2]。因此，通过使用具有这些突变的两种突变小鼠品系，我们试图在小鼠模型MRL/lpr和EOD中鉴定关键参与自身免疫性疾病发病机制的效应细胞和分子。1.信号淋巴细胞活化分子（SLAM）相关蛋白（SAP）在自身免疫性肝炎发生发展中的作用（Furukawa，Ono，石井）。结果提供了证据：（1）SAP具有抑制ConA诱导的肝炎发展的作用，（2）SAP的抑制作用取决于肝损伤的细胞功能，而与Fas配体（FasL）无关2. SLAM家族受体的特征与发展相关 ...更多信息 我们构建了SLAM家族受体在体内表达的DNA载体，并确定了每种表达构建体的流体静力学表达方法的最佳条件。本研究建立了C57 BL/6J-cinn/cinn（B6 ^），该品系小鼠Cuppuccino基因（Cno）功能缺失突变导致血小板功能缺陷。<cinn>与野生型小鼠相比，在B6 ^小鼠中观察到对被动IgE激发的过敏反应（IgE过敏反应）显著更高。<cinn>尤其在反应的后期，差异更明显。4.血小板在小鼠实验性和自发性关节炎（Ono）发生中的作用初步研究表明，B6 ^在胶原诱导的关节炎（CIA）中表现出抵抗表型，提示血小板在CIA的发生中具有抑制作用。<cinn>少

项目成果

Pleomorphic carcinoma of the lung associated with loss of heterozygosity of p53 gene

• DOI: 10.1620/tjem.206.181
• 发表时间: 2005-06-01
• 期刊: TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 2.2
• 作者: Arita, N;Mikami, Y;Ono, M
• 通讯作者: Ono, M

Genetic characterization of spontaneous ankylosing arthropathy with unique inheritance from Fas-deficient strains of mice

Fas 缺陷小鼠品系独特遗传的自发性强直性关节病的遗传特征

• 发表时间: 2006
• 期刊: Ann Rheum Dis 65
• 作者: Shiro Mori;Ming-Cai Zhang;Naoko Tanda;Fumiko Date;Masato Nose;Hiroshi Furukawa;Masao Ono
• 通讯作者: Masao Ono

Endothelial adhesion molecules in glomerular lesions: Association with their severity and diversity in lupus models

• DOI: 10.1111/j.1523-1755.2004.00537.x
• 发表时间: 2004-04-01
• 期刊: KIDNEY INTERNATIONAL
• 影响因子: 19.6
• 作者: Nakatani, K;Fujii, H;Nose, M
• 通讯作者: Nose, M

Avian flu : Influenza virus receptors in the human airway.

禽流感：人类呼吸道中的流感病毒受体。

• 发表时间: 2006
• 期刊: Nature 440
• 作者: Shinya K;Ebina M;Shinya Y;Ono M;Kasai N;Kawaoka Y
• 通讯作者: Kawaoka Y

Genetic characterization of spontaneous ankylosing arthropathy with unique inheritance from Fas-deficient strains of mice.

自发性强直性关节病的遗传特征，具有 Fas 缺陷小鼠品系的独特遗传。

• 发表时间: 2006
• 期刊: Ann Rheum Dis 65
• 作者: Mori S;et. al.
• 通讯作者: et. al.