Brain lipid composition in grey-lethal mutant mouse characterized by severe malignant osteopetrosis.
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.
Prinetti
Alessandro
A
Center of Excellence on Neurodegenerative Diseases, Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Milan, Italy. alessandro.prinetti@unimi.it
Rocchetta
Federica
F
Costantino
Elvira
E
Frattini
Annalisa
A
Caldana
Elena
E
Rucci
Francesca
F
Bettiga
Arianna
A
Poliani
Pietro L
PL
Chigorno
Vanna
V
Sonnino
Sandro
S
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
D005699:Galactosylceramides; D005732:Gangliosides; D020404:Glycerophospholipids; D008055:Lipids; D008565:Membrane Proteins; C509143:OSTM1 protein, mouse; D013107:Sphingolipids; D002784:Cholesterol
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