Adipocytes as endocrine cells and their roles in mice (PPARgamma knockout mice)
| Project/Area Number |
08557063
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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 | 展開研究 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Kobe University |
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Principal Investigator |
KASUGA Masato Kobe University, School of Medicine, Professor, 医学部, 教授 (50161047)
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| Co-Investigator(Kenkyū-buntansha) |
HORIKOSHI Hiroyoshi Sankyo Campany, The Biological Research Laboratories, 第一生物研究所, 次長
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 1997: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1996: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | PPARgamma / 3T3-L1 adipocytes / adenovirus vector / adipocyte differentiation / 3T3-L1脂肪細胞 / ドミナントネガティブ変異体 / PPARγ2 / PCR-SSCP |
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| Research Abstract |
To elucidate the physiological function of adipocytes in intact animals, we tried to make PPAR_<gamma> knockout mice. However, during our experiments, we were informed that PPAR_<gamma> knockout mice were embryonic lethal. therefore, we tried another approach. That is, adipose tissue-specific expression of dominant-negative mutants of PPAR_<gamma>, To find dominant-negative mutants of PPAR_<gamma>, we made several mutants and expressed in 3T3-L1 preadipocytes using adenovirus vector and found that the mutant, in which 16 amino acids in C-terminal were deleted, inhibited the adipocyte differentiation induced by thiazolidinedione. Therefore, this mutant may be useful to make fat-less mice by the transgenic method.
Since PPAR_<gamma> has an important role in adipocyte differentiation and systemic insulin action, functional defects in PPAR_<gamma> might be expected to result in the impaired adipogenesis and insulin resistance, conditiones typical of lipoatrophic diabetes. Therefore, we examined the mutation in the coding sequences of PPAR_<gamma> gene by PCR-SSCP and found that the coding sequences of the PPAR_<gamma> gene are normal in individuals with lipoatrophic diabetes.
Furthermore, we also examined the mutation in the coding sequences of the PPAR_<gamma> gene in individuals with type 2 diabetes and found the Prol2Ala mutations. However, the allele frequency of this mutation between normal and type2 diabetic patiants were not changed.
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Report
(3 results)
Research Products
(4 results)
