Study on the production of N-Glycolylneuraminic acid-deficient animals using gene targeting techniques

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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.