TY - JOUR
T1 - Brain lipid composition in grey-lethal mutant mouse characterized by severe malignant osteopetrosis
AU - Prinetti, Alessandro
AU - Rocchetta, Federica
AU - Costantino, Elvira
AU - Frattini, Annalisa
AU - Caldana, Elena
AU - Rucci, Francesca
AU - Bettiga, Arianna
AU - Poliani, Pietro L.
AU - Chigorno, Vanna
AU - Sonnino, Sandro
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - Demyelination
KW - Gangliosides
KW - Myelin
KW - Ostepetrosis
KW - Sphingolipids
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U2 - 10.1007/s10719-008-9179-8
DO - 10.1007/s10719-008-9179-8
M3 - Article
C2 - 18781385
AN - SCOPUS:67651150040
VL - 26
SP - 623
EP - 633
JO - Glycoconjugate Journal
JF - Glycoconjugate Journal
SN - 0282-0080
IS - 6 SPEC. ISS.
ER -