2005 Fiscal Year Final Research Report Summary
Study on the immunological mechanism of anti-TSH receptor antibody production by using transgenic mice
| Project/Area Number |
15590354
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Hoshi University Faculty of Pharmaceutical Science |
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Principal Investigator |
YOSHIDA Tadashi Hoshi University Faculty of Pharmaceutical Science, Dept of Pathophysiology, Professor, 薬学部, 教授 (00182767)
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| Co-Investigator(Kenkyū-buntansha) |
MUTO Akihiro Hoshi University Faculty of Pharmaceutical Science, Dept of Pathophysiology, Assistant Professor, 薬学部, 講師 (90239468)
KANEDA Toshio Hoshi University Faculty of Pharmaceutical Science, Dept of Pathophysiology, Instructor, 薬学部, 助手 (70339521)
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| Project Period (FY) |
2003 – 2005
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| Keywords | TSH receptor / Anti-TSH receptor antibody / Graves' disease / Animal model / Transgenic mice |
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| Research Abstract |
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.
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[Book] 疾患病態解析学2003
Author(s)
吉田正
Total Pages
37-80
Publisher
朝倉書店
Description
「研究成果報告書概要(和文)」より
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