Brief Communication | Published:

Successful prenatal mannose treatment for congenital disorder of glycosylation-Ia in mice

Nature Medicine volume 18, pages 7173 (2012) | Download Citation

Abstract

Congenital disorder of glycosylation-Ia (CDG-Ia, also known as PMM2-CDG) is caused by mutations in the gene that encodes phosphomannomutase 2 (PMM2, EC 5.4.2.8) leading to a multisystemic disease with severe psychomotor and mental retardation. In a hypomorphic Pmm2 mouse model, we were able to overcome embryonic lethality by feeding mannose to pregnant dams. The results underline the essential role of glycosylation in embryonic development and may open new treatment options for this disease.

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Acknowledgements

The work of C.K. and C.T. was supported by grants of the Deutsche Forschungsgemeinschaft (KO 2152/3-2 and TH1461/2-1) and the Fritz Thyssen Stiftung. The work of C.D. was supported by a US National Institutes of Health grant (R21 HD062914) and The Rocket Fund.

Author information

Affiliations

  1. Center for Child and Adolescent Medicine and Center for Metabolic Diseases Heidelberg, Department Kinderheilkunde I, Heidelberg, Germany.

    • Anette Schneider
    • , Christian Thiel
    • , Charles DeRossi
    • , Diana Popovici
    • , Georg F Hoffmann
    •  & Christian Körner
  2. Institut für Biochemie II, Göttingen, Germany.

    • Jan Rindermann
  3. German Cancer Research Center Heidelberg, Division of Cellular and Molecular Pathology, Heidelberg, Germany.

    • Hermann-Josef Gröne

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Contributions

A.S. and C.T. contributed equally, and were both responsible for experimental design, mouse experiments and data analysis, and they wrote the manuscript. J.R. generated mouse embryonic stem cell lines. C.D. and D.P. performed mouse dissections and histology. G.F.H. assisted in data analysis. H.-J.G. analyzed the histological data. C.K. supervised all aspects of this work, analyzed data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Christian Körner.

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    Supplementary Figures 1–4, Supplementary Tables 1 and 2 and Supplementary Methods

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DOI

https://doi.org/10.1038/nm.2548

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