Identification of type 2 diabetes genes on chromosome 2 of SMXA-5 mouse.
| Project/Area Number |
17380084
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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 |
Food science
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| Research Institution | Nagoya University (2006-2007)
Chubu University (2005) |
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Principal Investigator |
HORIO Fumihiko Nagoya University, Graduate School of Bioagricultural Sciences, Professor (20165591)
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| Co-Investigator(Kenkyū-buntansha) |
IKEGAMI Hiroshi Kinki University, School of Medicine, Professor (20221062)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥13,030,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2007: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2006: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2005: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | Type 2 diabetes / Disease model mouse / QTL analysis / Glucose tolerance / Diabetogenic gene / 耐糖性 / マウス |
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| Research Abstract |
Aims/hypothesis:
The SMXA-5 mouse is one of the SMXA recombinant inbred substrains established from the non-diabetic SM/J and A/J strains, and is a model for polygenic type2diabetes, characterised by moderately impaired glucose tolerance and hyperinsulinaemia. These diabetic traits are worsened by feeding a high-fat diet. The aim of this study was to dissect the diabetogenic loci in the A/J regions of the SMXA-5 genome that contribute to
diabetes-related traits and identify these diabetogenic genes.
Materials and methods:
We analysed the quantitative trait loci (QTL) for diabetes-related traits and obesity in (SM/JxSMXA-5) F2intercross mice fed a high-fat diet. To verify the function of the responsible locus that was mapped in the present study, we constructed 7 congenic strains and characterised their diabetes-related traits. Thereafter, we selected candidate genes for our diabetic locus.
Results:
A major QTL for glucose tolerance, free-fed blood glucose concentration and BMI was mapped on chromosome 2. This locus existed near D2Mit15, with the highest logarithm of the odds score (12.6) for glucose tolerance, and was designated T2dm2sa. The diabetogenic allele of T2dm2sa originated in the A/J strain. SM. A-T2dm2sa, a congenic strain that introgressed the T2dm2sa region of A/J genome into SM/J, exhibited overt impaired glucose tolerance and hyperinsulinaemia. Moreover, we established 6 subucongenic strains from this congenic strain, and analyzed their glucose tolerance. As a result, we clarified that one diabetogenic gene exist in the4Mb region (72-76Mb) on chromosome 2.
Conclusions/interpretation:
The development of impaired glucose tolerance in SM. A-T2dm2sa mice confirmed the results of QTL analysis for diabetes-related traits in F2 intercross mice. By subsequent analyses in subcongenic strains, we selected one candidate gene for T2dm2sa, which affects glucose tolerance.
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Ascorbic acid deficiency stimulates hepatic expression of inflammatory chemokine, cytokine-induced neutrophil chemoattractant-1, in scurvy-prone ODS rats.2006
Author(s)
Horio, F., Kiyama, K., Kobayashi, M., Kawai, K., Tsuda, T.
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Journal Title
J.Nutr.Sci.Vitaminol. 52(1)
Pages: 28-32
NAID
Related Report
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