1999 Fiscal Year Final Research Report Summary
Liver disorders in mice lacking transcription factors
| Project/Area Number |
09470047
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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 |
Pathological medical chemistry
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| Research Institution | Chiba University (1998-1999)
Kumamoto University (1997) |
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Principal Investigator |
TAKIGUCHI Masaki Chiba University, School of Medicine Professor, 医学部, 教授 (40179578)
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| Co-Investigator(Kenkyū-buntansha) |
HIWASA Takaki Chiba University, School of Medicine Associate Professor, 医学部, 助教授 (30260251)
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| Project Period (FY) |
1997 – 1999
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| Keywords | transcription factor / gene disrupted mice / metabolic disorder / CCAAT / enhancer-binding protein / C / EBP / ornithine cycle / hyperammonemia / hypoglycemia |
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| Research Abstract |
Gene disruption studies have produced a number of transcription factor-deficient mice, some of which are useful as model animals for human disorders. Recently, mice lacking members of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors were shown to exhibit a variety of liver disorders. To investigate pathophysiology and to develop therapy for these disorders, we examined abnormalities in expression of genes for ornithine cycle enzymes which detoxify ammonia in the liver.
Pathophysiology of C/EBPα-deficient mice- It has been reported that C/EBPα-deficient mice die within several hours after birth because of hypoglycemia resulting from insufficiency of expression of genes for gluconeogenic enzymes in the liver. We showed that the mice also exhibit hyperammonemia resulting from insufficiency of genes for ornithine cycle enzymes. Now we are examining whether induction of other members such as C/EBPβ by administration of glucocorticoids and cAMP can compensate C/EBPα-deficiency or not. In addition, we are investigating organ-specificity of the defficiency by examining whether expression of the gene for arginase, the last enzyme of the ornithine cycle, in salivary glands is affected or not.
Defects in hormone responsiveness of genes for ornithine cycle enzymes in C/EBPβ-deficient mice- We showed that in primary-cultured hepatocytes derived from C/EBPβ-deficient mice induction of genes for two enzymes of the cycle by glucocorticoids and glucagon are almost completely lost. Now we are examining whether the induction of genes for the enzymes in vivo is affected or not in fasting which augments effects of glucocorticoids and glucagon.
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Research Products
(31 results)
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[Publications] Tomomura, M., Tomomura, A., Musa, D. A. A., Horiuchi, M., Takiguchi, M., Mori, M., and Saheki, T.: "Suppressed expression of the urea cycle enzyme genes in the liver of carnitine-deficient juvenile visceral steatosis (JVS) mice in infancy and during starvation in adulthood."J. Biochem.. 121. 172-177 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Yoshida, E., Aratani, S., Itou, H., Miyagishi, M., Takiguchi, M., Osumi, T., Murakami, K., and Fukamizu, A.: "Functional association between CBP and HNF4 in trans-activation"Biochem. Biophys. Res. Commun.. 241. 664-669 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Sonoki, T., Nagasaki, A., Gotoh, T., Takiguchi, M., Takeya, M., Matsuzaki, H., and Mori, M.: "Coinduction of nitric-oxide synthase and arginase I in cultured rat peritoneal macrophages and rat tissues in vivo by lipopolysaccharide."J. Biol. Chem.. 272. 3689-3693 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamaguchi, Y., Ackerman, S. J., Minegishi, N., Takiguchi, M., Yamamoto, M., and Suda, T.: "Mechanisms of transcription in eosinophils : GATA-1, but not GATA-2, transactivates the promoter of the eosinophil granule major basic protein gene."Blood. 91. 3447-3458 (1998)
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[Publications] Kimura, T., Christoffels, V. M., Chowdhury, S., Iwase, K., Matsuzaki, H., Mori, M., Lamers, W. H., Darlington, G. J., and Takiguchi, M.: "Hypoglycemia-associated hyperammonemia caused by impaired expression of ornithine cycle enzyme genes in C/EBPα knockout mice."J. Biol. Chem.. 273. 27505-27510 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Miyanaka, K., Gotoh, T., Nagasaki, A., Takeya, M., Ozaki, M., Iwase, K., Takiguchi, M., Iyama, K., Tomita, K., and Mori, M.: "Immunohistochemical localization of arginase II and other enzymes of arginine metabolism in rat kidney and liver."Histochem. J.. 30. 741-751 (1998)
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[Publications] Iwase, K., Iyama, K., Akagi, K., Yano, S., Fukunaga, K., Miyamoto, E., Mori, M., and Takiguchi, M.: "Precise distribution of neuronal nitric oxide synthase mRNA in the rat brain revealed by non-radioisotopic in situ hybridization."Mol. Brain. Res.. 53. 1-12 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Braissant, O., Honegger, P., Loup, M., Iwase, K., Takiguchi, M., and Bachmann, C.: "Hyperammonemia : regulation of argininosuccinate synthetase and argininosuccinate lyase genes in aggregating cell cultures of fetal rat brain."Neurosci. Lett.. 266. 89-92 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Zhang, W. I., Takiguchi, M., Koshiyama, Y., Gotoh, T., Nagasaki, A., Iwase, K., Yamamoto, K., takeshima, H., Negi, A., and Mori, M.: "Expression of citrulline-nitric oxide cycle in lipopolysaccharide and cytokine-stimulated rat astroglioma C6 cells."Brain Res.. 849. 78-84 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Iwase, K., Miyanaka, K., Shimizu, A., Nagasaki, A., Gotoh, T., Mori, M., and Takiguchi, M.: "Induction of endothelial nitric oxide synthase in rat brain astrocytes by systemic lipopolysaccharide treatment."J. Biol. Chem.. 275(in press). (2000)
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「研究成果報告書概要(欧文)」より
