2005 Fiscal Year Final Research Report Summary
Association of glutamic acid antibody with the development and/or the progression of the disease in autoimmune type 1 diabetes mellitus
| Project/Area Number |
16590871
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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 |
Metabolomics
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| Research Institution | University of Yamanashi |
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Principal Investigator |
OMORI Masayuki University of Yamanashi, University of Yamanashi Hospital, Research Associate, 医学部附属病院, 助手 (40372502)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Shoichiro University of Yamanashi, University of Yamanashi Hospital, Medical Staff, 医学部附属病院, 医員 (70377521)
KOBAYASHI Tetsuro University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Professor, 大学院・医学工学総合研究部, 教授 (30113442)
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| Project Period (FY) |
2004 – 2005
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| Keywords | type 1 diabetes / knockout mice / glutamic acid decarboxylase 65 / autoantibody |
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| Research Abstract |
Autoimmune type 1 diabetes is composed of at least two clinical subtypes : acute onset form (acute onset type 1 [insulin-dependent] diabetes mellitus : AIDDM) and slowly progressive form (slowly progressive type 1 [insulin-dependent] diabetes mellitus : SPIDDM). Glutamic acid decarboxylase (GAD) 65 autoantibody (GAD65Ab), one of the diabetes-related autoantibodies, is detected in patients with SPIDDM and patients with AIDDM. However, the epitopes of GAD65Ab in SPIDDM are different from those in AIDDM : GAD65Ab in SPIDDM recognize the N-terminal residues of GAD65 molecule although GAD65Ab in AIDDM do not. This suggests that the difference of epitopes in GAD65Ab might cause different clinical courses between SPIDDM and AIDDM. Hence, we investigated the association of the difference of the epitopes in GAD65Ab with development and/or progression of type 1 diabetes using non-obese diabetes (NOD) mice.
Firstly, we tried to generate the mice that express the specific portion of GAD65 molecule in pancreatic beta-cells and lack the remaining portion of GAD65 molecule. For this purpose, we transferred rat-insulin promoter driven the N-terminal or C-terminal portion of GAD65 gene to embryo of GAD65 knockout NOD mice. However, we failed gene transfer to GAD65 knockout mice because of the nature of natural occurrence of diabetes in these mice.
Secondary, we scheduled administration of GAD65 protein fragments (the N-terminal residues and the C-terminal residues) to GAD65 knockout NOD mice. We obtained the C-terminal fragment of GAD65 molecules using prokaryotic expression systems although the N-terminal fragment was not obtained.
We are now administrating the C-terminal fragment of GAD65 molecules to GAD65 knockout mice and investigating the change on the rate of development to diabetes. We are also trying to generate the N-terminal fragment of GAD65 molecule using insect expression systems.
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Research Products
(9 results)
