Myelin Abnormalities in the Optic and Sciatic Nerves in Mice With GM1-Gangliosidosis

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 beta-galactosidase (beta-gal) +/? and (beta-gal) -/- mice, a model of GM1 gangliosidosis. Optic nerve weight was lower in the beta-gal -/- mice than in unaffected (beta-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 beta-gal -/- mice. The content of myelin-enriched cerebrosides, sulfatides, and plasmalogen ethanolamines was significantly lower in optic nerve of beta-gal -/- mice than in (beta-gal) +/? mice; however, cholesteryl esters were enriched in the beta-gal -/- mice. No major abnormalities in these lipids were detected in the sciatic nerve of the beta-gal -/- mice. The abnormalities in GM1 and myelin lipids in optic nerve of beta-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 beta-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 beta-gal -/- mice is likely due to the greater glycolipid storage in optic nerve.