| Project/Area Number |
16390264
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kinki University (2006)
Osaka University (2004-2005) |
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Principal Investigator |
IKEGAMI Hiroshi Kinki University, School of Medicine, Professor, 医学部, 教授 (20221062)
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| Co-Investigator(Kenkyū-buntansha) |
YAMATO Eiji Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (20273667)
FUJISAWA Tomomi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10324766)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | diabetes mellitus / gene / multifactorial disease / animal models / congenic strain / gene-gene interaction / gene-environment interaction |
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| Research Abstract |
To clarify genetic basis of diabetes mellitus for better understanding of molecular mechanisms of the disease pathogenesis and for the development of effective methods for prevention and intervention, molecular genetic studies on both type 1 and type 2 diabetes were performed in inbred animal models for type 1(NOD mice) and type 2 (NSY mice) diabetes, respectively with particular focus on gene-gene and gene-environmental interaction Analysis of consomic and congenic strains with NSY derived diabetogenic chromosomes introgressed onto control C3H/He genetic background revealed the existence of diabetogenic genes on mouse chromosome 11 and 14, respectively. Gene-gene interaction was demonstrated for obesity between chromosomes 11 and 14. Diabetogenic genes on both chromosomes 11 and 14 showed gene-environment interaction with markedly deteriorated phenotypes with supplementation of 30% sucrose in drinking water. Sub-congenic analysis demonstrated that diabetogenic genes on chromosome 11 consist of multiple components.
Sub-congenic analysis of NOD mice congenic for Iddl6 region on chromosome 17 revealed that Iddl6 consists of multiple components and one of them is located in class I K region.
Multi-center collaborative study team, termed the Japanese Study Group on Type 1 Diabetes Genetics was established and made it possible to perform large-scale genetic association studies with sufficient power on candidate genes for type 1 diabetes. Taking advantage of these valuable resources, contribution of INS, CTLA4, PTPN22 and SUMO4 on susceptibility to type 1 diabetes in Japanese was confirmed. The data generated from the present study provides valuable information on genetics of diabetes for future development of tailored medicine in the treatment of diabetes mellitus.
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