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

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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Figure 1: Microscopic, biochemical and histochemical examinations of Pmm2+/+ and Pmm2R137H/F118L embryos.
Figure 2: Histological and WGA lectin binding analyses of mannose-supplemented Pmm2+/+ and Pmm2R137H/F118L embryos 16.5 d.p.c.

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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.

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Authors

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.

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Correspondence to Christian Körner.

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The authors declare no competing financial interests.

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Supplementary Figures 1–4, Supplementary Tables 1 and 2 and Supplementary Methods (PDF 2619 kb)

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Schneider, A., Thiel, C., Rindermann, J. et al. Successful prenatal mannose treatment for congenital disorder of glycosylation-Ia in mice. Nat Med 18, 71–73 (2012). https://doi.org/10.1038/nm.2548

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