Study on the immunological mechanism of anti-TSH receptor antibody production by using transgenic mice
转基因小鼠产生抗TSH受体抗体的免疫学机制研究
基本信息
- 批准号:15590354
- 负责人:
- 金额:$ 2.24万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2003
- 资助国家:日本
- 起止时间:2003 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
In Graves' disease, autoantibody directed against TSH receptor (TSHR) mimic the action of TSH and are therefore called thyroid-stimulating antibody (TSAb). TSAb caused overstimulation of the thyroid gland and hyperthyroidism. Animal models are very useful tools to clarify the pathophysiology of autoimmune thyroid disease.Recently, several animal models of Graves' disease have been developed, some of which employed genetic immunization. A transgenic mouse line that expresses Cre recombinase under control of the human keratinocyte gene promoter was established. The activity and specificity of the keratin-driven Cre recombinase were examined by using Northern blotting. This keratin-Cre transgenic mouse was specifically delete loxP-inserted lac Z gene in keratinocytes and induced TSHR gene during development and/or in adult keratinocytes. However, we could not detect the activities of anti-TSHR antibody and high levels of serum thyroid hormone.We then used the technique of electroporation (EP) for establishment of a new model of Graves' disease in expectation of greatly enhanced hTSHR expression in vivo. Among non-viral techniques for gene transfer by plasmid vector in vivo, the method with direct injection of plasmid DNA into muscles is simple, while is restricted by the relatively low expression levels of the transferred gene.Moreover, we established hTSHR expressing stable clone (AHK12), having functional response to bTSH, for the detection of biological activity of autoantibody and ELISA for the detection of autoantibody against rhTSHR-289His, corresponding to the extracellular A subunit TSHR.
在Graves病中,针对TSH受体的自身抗体(TSHR)模拟TSH的作用,因此称为甲状腺刺激抗体(TSAb)。TSAb引起甲状腺过度刺激和甲状腺功能亢进。动物模型是阐明自身免疫性甲状腺疾病病理生理机制的重要工具,近年来已建立了几种Graves病动物模型,其中一些采用了基因免疫。建立了在人角质形成细胞基因启动子控制下表达Cre重组酶的转基因小鼠系。通过使用北方印迹检测角蛋白驱动的Cre重组酶的活性和特异性。该转基因小鼠在角质形成细胞中特异性地缺失loxP插入的lac Z基因,并在发育期间和/或在成年角质形成细胞中诱导TSHR基因。然而,我们没有检测到抗TSHR抗体的活性和高水平的血清甲状腺激素,因此,我们使用电穿孔(EP)技术建立了一种新的Graves病模型,期望在体内大大提高hTSHR的表达。在非病毒的质粒载体体内基因转移技术中,直接肌肉注射质粒DNA的方法操作简单,但受转染基因表达水平相对较低的限制,我们建立了hTSHR稳定表达克隆(AHK 12),对bTSH有功能反应,用于检测自身抗体的生物学活性和ELISA用于检测针对rhTSHR-289 His(对应于细胞外A亚基TSHR)的自身抗体。
项目成果
期刊论文数量(52)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
MTX療法におけるアフター性口内炎に対するマレイン酸イルソグラジンの効果、リウマチ科
马来酸伊索拉定对MTX治疗后遗症性口腔炎的影响,风湿科
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:吉田正;Yoshida T.;吉田 正;吉田正;吉田正
- 通讯作者:吉田正
骨・関節の疾患、薬と疾病、II
骨关节疾病、药物与疾病II
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:吉田正;Yoshida T.;吉田 正;吉田正;吉田正;Yoshida T.;吉田 正;Yoshida T. et al.;Yoshida T. et al.;吉田正;Yoshida T. et al.;Yoshida T.;吉田正;吉田正;吉田正;吉田 正
- 通讯作者:吉田 正
ファーマシューティカルノート
医药笔记
- DOI:
- 发表时间:2003
- 期刊:
- 影响因子:0
- 作者:吉田正;Yoshida T.;吉田 正;吉田正;吉田正;Yoshida T.;吉田 正;Yoshida T. et al.;Yoshida T. et al.;吉田正;Yoshida T. et al.;Yoshida T.;吉田正;吉田正;吉田正;吉田 正;吉田 正;吉田正;吉田 正;吉田正;吉田正
- 通讯作者:吉田正
Prospective study of high-dose intravenous immunoglobulin for the treatment of steroid-resistant polymyositis and dermatomyositis.
大剂量静脉注射免疫球蛋白治疗类固醇抵抗性多发性肌炎和皮肌炎的前瞻性研究。
- DOI:
- 发表时间:2003
- 期刊:
- 影响因子:0
- 作者:吉田正;Yoshida T.;吉田 正;吉田正;吉田正;Yoshida T.;吉田 正;Yoshida T. et al.;Yoshida T. et al.
- 通讯作者:Yoshida T. et al.
慢性疾患薬物療法のツボ : 関節リウマチ
慢性病药物治疗要点:类风湿性关节炎
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:吉田正;Yoshida T.;吉田 正;吉田正;吉田正;Yoshida T.;吉田 正;Yoshida T. et al.;Yoshida T. et al.;吉田正;Yoshida T. et al.;Yoshida T.;吉田正;吉田正;吉田正
- 通讯作者:吉田正
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YOSHIDA Tadashi其他文献
YOSHIDA Tadashi的其他文献
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{{ truncateString('YOSHIDA Tadashi', 18)}}的其他基金
Role of KLF4 on phosphate-induced vascular calcification and cardiovascular diseases
KLF4在磷酸盐诱导的血管钙化和心血管疾病中的作用
- 批准号:
24591239 - 财政年份:2012
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Establishment of an antigen-specific immune regulating method by using food antigens
利用食物抗原建立抗原特异性免疫调节方法
- 批准号:
23580159 - 财政年份:2011
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Prevention of allergy by the regulation of B cell functions
通过调节B细胞功能预防过敏
- 批准号:
20780092 - 财政年份:2008
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Mechanism of heme degradation by heme oxygenase and the interaction of heme
血红素加氧酶降解血红素的机制及血红素的相互作用
- 批准号:
14580641 - 财政年份:2002
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A Study on the Publications of Science Books relating to Dutch Studies
荷兰研究相关科普书籍出版情况研究
- 批准号:
13021205 - 财政年份:2001
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Relation between the structure and the oxygen acitivation of heme oxygenase reaction
血红素加氧酶反应的结构与氧活化的关系
- 批准号:
12680625 - 财政年份:2000
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
REGULATION OF EXPRESION OF THE HUMAN THYROTROPIN RECEPTOR AND FUNCTIONAL ANALYSIS OF THE PROMOTER OF THE GENE
人促甲状腺激素受体的表达调控及基因启动子的功能分析
- 批准号:
10671042 - 财政年份:1998
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Mechanism of heme degradation by heme oxygenase
血红素加氧酶降解血红素的机制
- 批准号:
10044233 - 财政年份:1998
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (A).
Molucular mechanisms of oxygen activation at the three steps in heme oxygenase reaction
血红素加氧酶反应三步氧活化的分子机制
- 批准号:
09480158 - 财政年份:1997
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular mechanism of heme degradation catalyzed by heme oxygenase
血红素加氧酶催化血红素降解的分子机制
- 批准号:
08044240 - 财政年份:1996
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for international Scientific Research
相似海外基金
Studies on Diversity of Anti-TSH Receptor Antibody by Gene Technology.
利用基因技术研究抗TSH受体抗体多样性。
- 批准号:
63570546 - 财政年份:1988
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)