title: Brain lipid composition in grey-lethal mutant mouse characterized by severe malignant osteopetrosis.
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.
authors.affiliation: Center of Excellence on Neurodegenerative Diseases, Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Milan, Italy. alessandro.prinetti@unimi.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Prinetti
authors.forename: Federica
authors.initials: F
authors.lastname: Rocchetta
authors.forename: Elvira
authors.initials: E
authors.lastname: Costantino
authors.forename: Annalisa
authors.initials: A
authors.lastname: Frattini
authors.forename: Elena
authors.initials: E
authors.lastname: Caldana
authors.forename: Francesca
authors.initials: F
authors.lastname: Rucci
authors.forename: Arianna
authors.initials: A
authors.lastname: Bettiga
authors.forename: Pietro L
authors.initials: PL
authors.lastname: Poliani
authors.forename: Vanna
authors.initials: V
authors.lastname: Chigorno
authors.forename: Sandro
authors.initials: S
authors.lastname: Sonnino
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D005699:Galactosylceramides / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D020404:Glycerophospholipids / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism; D010022:Osteopetrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D013107:Sphingolipids / Q000378:metabolism
chemical_list: D005699:Galactosylceramides; D005732:Gangliosides; D020404:Glycerophospholipids; D008055:Lipids; D008565:Membrane Proteins; C509143:OSTM1 protein, mouse; D013107:Sphingolipids; D002784:Cholesterol
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