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Brain lipid composition in grey-lethal mutant mouse characterized by severe malignant osteopetrosis

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Abstract

The grey-lethal mouse (gl/gl) mutant most closely resembles the severe human malignant autosomal recessive OSTM1-dependent form of osteopetrosis that it has been described to be associated with neurological abnormalities. For this reason, we have analyzed the brain lipid composition (gangliosides, neutral glycosphingolipids, phospholipids and cholesterol), from gl/gl mice at different ages of development and compared with wild type mice. Both cholesterol and glycerophospholipid content and pattern in the gl/gl and control mice were very similar. In contrast, significant differences were observed in the content of several sphingolipids. Higher amount of the monosialogangliosides GM2 and GM3, and lower content of sphingomyelin, sulfatide and galactosylceramide were observed in the gl/gl brain with respect to controls. The low content of sphingomyelin, sulfatide and galactosylceramide is consistent with the immunohistochemical results showing that in the grey-lethal brain significant depletion and disorganization of the myelinated fibres is present, thus supporting the hypothesis that loss of function of the OSTM1 causes neuronal impairment and myelin deficit.

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Abbreviations

gl/gl :

grey-lethal

ARO:

Autosomal Recessive Osteopetrosis

OSTM1:

osteopetrosis associated transmembrane protein 1

HSC:

haematopoietic stem cells

HPTLC:

high-performance thin layer chromatography

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Acknowledgements

This work was supported by University of Milan (FIRST to S.S.), CARIPLO Foundation (to S.S.) and by Mitzutani Foundation for Glycoscience (to A.P.).

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Authors and Affiliations

  1. Center of Excellence on Neurodegenerative Diseases, Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Milano, Italy

    Alessandro Prinetti, Federica Rocchetta, Vanna Chigorno & Sandro Sonnino

  2. Institute of Biomedical Technologies, CNR, Milano, Italy

    Elvira Costantino, Annalisa Frattini, Elena Caldana & Arianna Bettiga

  3. Institute Clinico Humanitas, Rozzano, Italy

    Annalisa Frattini & Elena Caldana

  4. Division of Immunology, Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Francesca Rucci

  5. Institute of Molecular Medicine, University of Brescia, Brescia, Italy

    Pietro L. Poliani

  6. Via Fratelli Cervi 93, 20090, Segrate, Milan, Italy

    Alessandro Prinetti

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  1. Alessandro Prinetti
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  2. Federica Rocchetta
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Correspondence to Alessandro Prinetti.

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Prinetti, A., Rocchetta, F., Costantino, E. et al. Brain lipid composition in grey-lethal mutant mouse characterized by severe malignant osteopetrosis. Glycoconj J 26, 623–633 (2009). https://doi.org/10.1007/s10719-008-9179-8

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