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Reduced sialylation status in UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE)-deficient mice

Glycoconjugate Journal volume 24, pages 125–130 (2007)Cite this article

Abstract

Sialic acids are widely expressed as terminal carbohydrates on glycoconjugates of eukaryotic cells. They are involved in a variety of cellular functions, such as cell adhesion or signal recognition. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), which catalyzes the first two steps of sialic acid biosynthesis in the cytosol. Previously, we have shown that inactivation of the GNE by gene targeting causes early embryonic lethality in mice, whereas heterozygous GNE-deficient mice are vital. In this study we compared the amount of membrane-bound sialic acids of wildtype mice with those of heterozygous GNE-deficient mice. For that we quantified membrane-bound sialic acid concentration in various organs of wildtype- and heterozygous GNE-deficient mice. We found an organ-specific reduction of membrane-bound sialic acids in heterozygous GNE-deficient mice. The overall reduction was 25%. Additionally, we analyzed transferrin and polysialylated neural cell adhesion molecule (NCAM) by one- or two-dimensional gel electrophoresis. Transferrin-expression was unchanged in heterozygous GNE-deficient mice; however the isoelectric point of transferrin was shifted towards basic pH, indicating a reduced sialylation. Furthermore, the expression of polysialic acids on NCAM was reduced in GNE-deficient mice.

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Acknowledgements

We are grateful to Dr. C. Kannicht (Octapharma, Berlin) for help with the two-dimensional gel electrophoresis. This work received financial support by the Deutsche Forschungsgemeinschaft, the Hertie-Stiftung, the Sonnenfeld-Stiftung and the Fonds der Chemischen Industrie.

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  1. Institut für Physiologische, Chemie Hollystr. 1, 06114, Halle (Saale), Germany

    Daniel Gagiannis, André Orthmann, Ilona Danßmann, Martina Schwarzkopf, Wenke Weidemann & Rüdiger Horstkorte

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  1. Daniel Gagiannis
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  2. André Orthmann
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  3. Ilona Danßmann
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  4. Martina Schwarzkopf
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  5. Wenke Weidemann
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  6. Rüdiger Horstkorte
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Correspondence to Rüdiger Horstkorte.

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Daniel Gagiannis and André Orthmann have contributed equally to this work.

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Gagiannis, D., Orthmann, A., Danßmann, I. et al. Reduced sialylation status in UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE)-deficient mice. Glycoconj J 24, 125–130 (2007). https://doi.org/10.1007/s10719-006-9019-7

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  • DOI: https://doi.org/10.1007/s10719-006-9019-7

Keywords

  • (Poly)-Sialic acid
  • Transferrin
  • Neural cell adhesion molecule
  • Cell surface
  • Membranes