2006 Fiscal Year Final Research Report Summary
Identification of type 2 diabetes mellitus susceptibility candidate genes in loci detected by QTL analysis of diabetic db mice,
| Project/Area Number |
16390265
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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 | The University of Tokushima |
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Principal Investigator |
ITAKURA Mitsuo The University of Tokushima, Institute for Genome Research, Professor, ゲノム機能研究センター, 教授 (60134227)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Hiroshi The University of Tokushima, Institute for Genome Research, Research associate, ゲノム機能研究センター, 助教授 (20294639)
MORITANI Maki The University of Tokushima, Institute for Genome Research, Research assistant, ゲノム機能研究センター, 学術研究員 (50301312)
KUNIKA Kiyoshi The University of Tokushima, Institute for Genome Research, Research assistant, ゲノム機能研究センター, 学術研究員 (30396254)
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| Project Period (FY) |
2004 – 2006
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| Keywords | QTL / Lep^<db> mice / congenic mice / type 2 diabetes mellitus / susceptibility gene / congenic sub-line / animal model of diabetes / fat pad weight |
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| Research Abstract |
We previously mapped four major quantitative trait loci (QTLs) for type 2 diabetes mellitus (T2D), which affect T2D phenotypes in F_2 populations generated from a BKS.Cg-m+ /+ Lepr^<db> and C3H or DBA2 (D2) intercross. To identify the disease-susceptibility genes of T2D, we mapped the region using congenic mice. Our findings are as follows ; 1) We generated congenic mice by repeated backcross of donor (db) mice to recipient mice of D2 strain carrying a given QTL-containing genome region to test the effect of each QTL on diabetic phenotypes. Out of four QTLs, introgression of two regions of D2 mice was significantly different from that of control mice carrying BKS alleles. Differences in phenotypes were replicated in body weight, fat pad weight, fasting BG concentrations, and insulin level (A region) ; body weight, fat pad weight, and total cholesterol level (B region). 2) We generated 16 (for A region) or 22 (for B region) congenic sub-lines derived from BKS/D2 congenic region for two QTLs to facilitate fine mapping. 3) Analyses of seven sub-lines in one congenic mouse identified the region of three Mb, which affects body weight, fat pad weight in A region. Analyses of five sub-lines in another congenic mouse revealed the region of eight Mb, which affects body weight and fat pad weight in B region. However, we could not map the region correlating fasting BG concentrations in A region. These congenic sub-lines offered a powerful tool for fine mapping phenotypes-assigned QTL region. To identify the target gene, mRNA and protein expression analyses in various tissues from subcongenic and control mice are under way in our laboratory.
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[Book] ゲノムと疾患2004
Author(s)
板倉 光夫
Total Pages
214
Publisher
南山堂
Description
「研究成果報告書概要(和文)」より
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