| Project/Area Number |
12470226
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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 | Tokyo Woman's Medical University (2001)
The University of Tokyo (2000) |
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Principal Investigator |
GOTODA Takanari Tokyo Women's Medical University, Internal Medicine, Lecturer, 医学部, 講師 (60322062)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Nobuhiro Tsukuba University, Internal Medicine, Professor, 医学部, 教授 (40200729)
OHASHI Ken University of Tokyo, Internal Medicine, Medical stuff, 医学部, 医員
ISHIBASHI Shun Jichi Medical University, Internal Medicine, Professor, 医学部, 教授 (90212919)
SUDOH Takako Tokyo Women's Medical University, Internal Medicine, Assistant professor, 医学部, 助手
IWAMOTO Yasuhiko Tokyo Women's Medical University, Internal Medicine, Professor, 医学部, 教授 (60143434)
大須賀 淳一 東京大学, 医学部・附属病院, 医員
島野 仁 東京大学, 医学部・附属病院, 助手
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 2001: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2000: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | Insulin resistance / Animal model / Gene / QTL / Chromosome 9 / SHR / QTL解析 / ラット / 高血圧 / キヌレニン |
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| Research Abstract |
SHR is a genetic model of human insulin resistance syndrome (IRS). Quantitative trait loci (QTLs) for IRS-related phenotypes have been mapped to the regions on rat chromosomes (Chrs) 3, 4 and 12. Interestingly, multiple QILs have been shown to cluster around a single region on either Chr 3 or 4. In SHR strains derived from the NIH, USA, a deletional mutation has been identified in the Cd36 located within the Chr 4-QTL region. The mutation was, however, absent in the Cd36 of the original SHR strains and was shown to be introduced during breeding at the NIH. Comparison between SHR strains indicated that the Cd36 mutation is unlikely to be a major cause of insulin resistance phenotypes in SHR. QTLs for hypertension, reduced adiposity and insulin resistance in SHR, as well as a candidate gene (KAT-1) locus, have been mapped to an overlapping region of the proximal end of rat Chr 3. We have identified a functional missense mutation in the KAT-1 derived from all SHR strains examined. The chromosomal localization of the human homologue of KAT-1 to human Chr 9q22, where diabetes, hypertension and obesity have previously been linked, warrants further investigation of the homologue of KAT-i in humans.
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