| Project/Area Number |
10470144
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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 |
Gastroenterology
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| Research Institution | University of Occupational and Environmental Heath |
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Principal Investigator |
OTSUKI Makoto University of Occupational and Enviromental Health, School of Medicine, Third Department of Internal Medicine, Professor, 医学部, 教授 (00030916)
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| Co-Investigator(Kenkyū-buntansha) |
KIHARA Yasuyuki University of Occupational and Environmental Health, School of Medicine, Third Department of Internal Medicine, Research Associate, 医学部, 助手 (80279330)
NAKAMURA Hayato University of Occupational and Environmental Health, School of Medicine, Third Department of Internal Medicine, Assistant Professor, 医学部, 講師 (90207902)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥9,100,000 (Direct Cost: ¥9,100,000)
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| Keywords | OLETF rat / transgenic rat / CCK-A receptor / ノックアウトラット |
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| Research Abstract |
Otsuka Long-Evans Tokushima Fatty (OLETF) rats developed at the Tokushima Reseach Institute (Otsuka Pharmaceutical, Tokushima, Japan) are a new inbred animal model of type 2 diadetes mellitus with polyuria, polydipsia, and mild obesity. After a chronic course of hyperglycemia with hyperinsulinemia and mild obesity, OLETF rats eventually become hyoinsulinemic and develop insulin-dependent (type 2) diadetes mellitus like diabetes. We have reported that OLETF rats have CCK-A receptor gene anomalies and deficient CCK-A receptor-mediated biological function in the pancreas, stomach and brain.
To examine the effect of the overexpressed CCK-A receptor on OLETF rats, we planed to generate transgenic OLETF rats expressing CCK-A receptor. Rat CCK-A receptor cDNA was amplified using first-strand cDNA as a template, and cloned in the pSI vector (Promega Corporation). The nucleotide sequence of the PCR product was identical to the reported sequence of the rat CCK-A receptor cDNA.The expression vector including the SV40 enhancer/early promoter for transgenic rat was constructed, and rat CCK-A receptor cDNA was inserted into its cloning site flanking the exon-intron organization and a polyadenlation signal of the rabbit β-globin gene. We obtained 17 CCK-A receptor transgenic OLETF rats. We would like to examine phenotypes of the CCK-A receptor transgenic OLETF rats in the future.
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