| Project/Area Number |
14380384
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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 |
Laboratory animal science
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MATSUMOTO Kozo The University of Tokushima, Institute of Health Biosciences, Division for Animal Research Resources, Associate Professor, 大学院・ヘルスバイオサイエンス研究部, 助教授 (00002246)
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| Co-Investigator(Kenkyū-buntansha) |
KOSE Hiroyuki The University of Tokushima, Institute of Health Biosciences, Division for Animal Research Resources, Assistant Professor, 大学院・ヘルスバイオサイエンス研究部, 助手 (90314856)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | type 2 diabetes / congenic rat / sub-congenic strains / OLETF rat / obesity / proteome / congenic stra / sub-congenic starains / obesity / gene / OLETF / rat / QTL / congenic strain |
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| Research Abstract |
Linkage analysis previously identified a hyperglycemic quantitative trait locus (QTL), Nidd2/of, on rat Chromosome 14 in crosses utilizing OLETF (Otsuka Long Evans Tokushima Fatty) rat, a model for type2 diabetes. A separate QTL study mapped an obesity QTL, Obs5, to the same chromosomal region. A congenic strain placing ca. 38 cM OLETF-derived segments containing both Nidd2/of and Obs5 on the F344 background was shown to possess mild diabetic and obese phenotypes, suggesting the presence of mutations affecting the glucose metabolism and fat accumulation. In order to localize the loci more precisely, we generated a series of deletion-subcongenic strains in which OLETF-segments were shortened from either ends. We found that there are at least two hyperglycemic QTL within the Nidd2/of locus. We predict that they are localized towards both ends of the Nidd2/of region. In contrast, Obs5 QTL was further narrowed down to a single region of ca. 10 cM fragment.
Understanding the genetic bases of
… More
complex disease requires not only the identification of disease causative genes, but also the precise description of interactions among genes involved. Previously we identified hyperglyceamic QTLs in OLETF rats, which were subsequently verified by examining congenic rats possessing each locus individually. In this study, we constructed a double congenic strain introgressing Nidd1/of and Nidd2/of loci. OGTT analysis revealed that the double congenic rats showed acute glucose elevation presumably due to the effect of Nidd2/of followed by sustained hyperglycemia via the effect of Nidd1/of. This suggested that there was a characteristic difference between these loci. Nidd1/of was critical for late-phase glucose regulation during OGTT, while Nidd2/of played a more important role in early-phase. Furthermore, they interacted synergistically for the expression of hyperglycemia, indicating an epistatic interaction. Therefore congenic animals derived from complex disease model are tremendous resources for the study of common diseases. Less
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