| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Whereas predisposition to type 1 diabetes mellitus is determined by multiple genetic components, major histocompatibility complex (NHC)-linked genetic component is the strongest factor both in human and NOD mouse, an animal model for type 1 diabetes. By investigating a congenic NOD. CTS-H-2 line whose congenic interval is derived from the CTS mouse that has the identical MHC class II to the NOD mouse, we have shown that the mouse strong MHC-linked susceptibility is due to a combined effect of multiple genes and NOD has susceptibility gene outside class II region, termed Idd16. In the present project, we have clarified the following points ;
1, By expanding the congenic line from the frozen embryo, the type 1 diabetes in the congenic NOD. CTS-H-2 line was suppressed about one fourth to NOD mouse.
2, We established, by selective breeding, two subcongenic lines with new recombinant chromosomes found in the backcross progenies (F17 and F21), allowing fine mapping of Idd16 by comparison of the development of diabetes among the subcongenic lines.
3, As a candidate for Idd16, genome sequence of the MHC class I K gene of NOD and CTS mice was determined and K protein was investigated. The results indicated that K gene of the CTS was unique and suggested that K gene is responsible for Idd16.
4, Human SLC11A1 gene was investigated since mouse Slc11a1 gene was suggested as responsible for Idd5.2. We demonstrated through association study and a meta-analysis that a functional polymorphism in the Z-DNA forming motif in the promoter of the SLC11A1 gene is associated with type 1 diabetes across the races.
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