title: Myelin abnormalities in the optic and sciatic nerves in mice with GM1-gangliosidosis.
abstract: GM1-gangliosidosis is a glycosphingolipid lysosomal storage disease involving accumulation of GM1 and its asialo form (GA1) primarily in the brain. Thin-layer chromatography and X-ray diffraction were used to analyze the lipid content/composition and the myelin structure of the optic and sciatic nerves from 7- and 10-month old β-galactosidase (β-gal) +/? and β-gal -/- mice, a model of GM1gangliosidosis. Optic nerve weight was lower in the β-gal -/- mice than in unaffected β-gal +/? mice, but no difference was seen in sciatic nerve weight. The levels of GM1 and GA1 were significantly increased in both the optic nerve and sciatic nerve of the β-gal -/- mice. The content of myelin-enriched cerebrosides, sulfatides, and plasmalogen ethanolamines was significantly lower in optic nerve of β-gal -/- mice than in β-gal +/? mice; however, cholesteryl esters were enriched in the β-gal -/- mice. No major abnormalities in these lipids were detected in the sciatic nerve of the β-gal -/- mice. The abnormalities in GM1 and myelin lipids in optic nerve of β-gal -/- mice correlated with a reduction in the relative amount of myelin and periodicity in fresh nerve. By contrast, the relative amount of myelin and periodicity in the sciatic nerves from control and β-gal -/- mice were indistinguishable, suggesting minimal pathological involvement in sciatic nerve. Our results indicate that the greater neurochemical pathology observed in the optic nerve than in the sciatic nerve of β-gal -/- mice is likely due to the greater glycolipid storage in optic nerve.
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, USA.
authors.forename: Karie A
authors.initials: KA
authors.lastname: Heinecke
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, USA Department of Biochemistry and Molecular Biology, Committee on Immunology, University of Chicago, IL, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Luoma
authors.affiliation: Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: d'Azzo
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Kirschner
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, USA seyfridt@bc.edu.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Seyfried
mesh_terms: D000818:Animals; D002855:Chromatography, Thin Layer; D003720:Densitometry; D016537:Gangliosidosis, GM1 / Q000235:genetics* / Q000473:pathology*; D005838:Genotype; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology*; D009900:Optic Nerve / Q000166:cytology* / Q000473:pathology*; D012584:Sciatic Nerve / Q000473:pathology*; D014961:X-Ray Diffraction; D001616:beta-Galactosidase / Q000172:deficiency* / Q000235:genetics
chemical_list: D001616:beta-Galactosidase
keywords: X-ray diffraction; cerebrosides; gangliosides; lipids