| Project/Area Number |
17200029
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Central Institute for Experimental Animals |
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Principal Investigator |
YOSUYUKI Ohnishi Central Institute for Experimental Animals, Oncology Laboratory, Group director (70201382)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Haruo Central Institute for Experimental Animals, Animal Model laboratory, Researcher (30353478)
HIOKI Kyoji Central Institute for Experimental Animals, Animal Model laboratory, Head (80208735)
TOBE Kazuyuki Toyama Univ. School Med., Dept Med., Professor (30251242)
AMI Toshiro Nippon Animal Science Univ., Dept Physiological Chemistry, Professor (70184257)
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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 |
¥41,210,000 (Direct Cost: ¥31,700,000、Indirect Cost: ¥9,510,000)
Fiscal Year 2007: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2006: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
Fiscal Year 2005: ¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
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| Keywords | type 2 diabetes / TRS-2 / strain / translational research / insulin resistance / 系統 / PPAR / 糖尿病 / 実験動物 / ノックアウトマウス / 遺伝的背景 / 体外受精 / 自然交配 |
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| Research Abstract |
The aim of this project is to establish an animal experimentation system expecting to progress translational research for type 2 diabetes disease. Type 2 diabetes considers as one of multiple risk factors for other lifestyle-related] diseases, and many factors influence for the disease such as genetic and environmental contribution. Therefore, we set up genetic background with strict congenic conditions. Knockout (KO) mice for IRS1 gene and IRS2 gene were bred into C57BU6 (B6) strain respectively. We also bred with 129 strains for those gene knockdown mice. The earlier onset of diabetic symptoms such as hyper blood glucose levels, intolerance in GTT (glucose tolerance test) and resistance in'Tr (insulin tolerant test) were observed in B6-IRS2 KO than original hybrid strain. B6-IRS2 KO mice caused diabetic in six weeks of age. There were any obvious phenotypic difference observed between mice delivered by natural mating and those by using in vitro fertilization and embryo transfer technology. B6-IRS2 KO mice were fed three types of foods containing with 5%, 10% and 15% of fat, respectively. Progression of the disease was observed on GTT in the group with 10% fat, and both on GTT and ITT in the 15% fat-feeding group. Clinical value of GTT was getting worse in 129-IRS2 KO mice than those of B6 background. On the other hand, 129-IRS2 KO mice showed relatively good response against insulin treatment.
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