Project/Area Number |
07557155
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Biological pharmacy
|
Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
KAWASAKI Toshisuke Department of Biological Chemistry, Kyoto University, Professor, 薬学研究科, 教授 (50025706)
|
Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Makoto Central Laboratory, Kirin Brewery Co., Ltd., 主任研究員
SUZUKI Akemi Tokyo Metropolitan Institute of Medical Science, 部長 (70134533)
KOZUTSUMI Yasunori Dept.of Biol.Chem., Kyoto University, Assistant Professor, 薬学研究科, 助教授 (70205425)
|
Project Period (FY) |
1995 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥19,800,000 (Direct Cost: ¥19,800,000)
Fiscal Year 1997: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1996: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1995: ¥8,300,000 (Direct Cost: ¥8,300,000)
|
Keywords | carbohydrate antigen / CMP-NeuAc hydroxylase / N-Glycolylneuraminic acid / HD antigen / gene targeting / 遺伝子クローニング / ノックアウトマウス / クローニング |
Research Abstract |
N-Glycolylneuraminic acid (NeuGc) is derived from NeuAc by hydroxylation of a methyl moiety in the N-acetyl residue. This hydroxylation occurs by the conversion of CMP-N-acetylneuraminic acid (CMP-NeuAc) to CMP-N-glycolylCMP-NeuGc, which is carried out by an electron transport system involving NADH-dependent cytochrome b5 reductase, cytochrome b5, and CMP-NeuAc hydroxylase. CMP-NeuAc hydroxylase is the key enzyme in the hydroxylation of CMP-NeuAc, and functions at the final step of the electron transport system. We have previously purified CMP-NeuAc hydroxylase from the mouse liver, and isolated a cDNA for this enzyme which contains an ORF encoding a protein of 577 amino acids. All mammals examined except human have NeuGc and therefore NeuGc is known to be an epitope of one of major carbohydrate antigens in human. Recently, it is reported that NeuGc is detected in the sialic acid-containing medicines such as human erythropoietin produced in CHO cells. In this study, we plan to make NeuGc-deficient animals using gene-targeting technique in order to produce NeuGc-free tsialic acid-containing medicines.
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