Myelin abnormalities in mice deficient in galactocerebroside and sulfatide

Myelin sheath formation depends on appropriate axo-glial interactions that are mediated by myelin-specific surface molecules. In this study, we have u sed quantitative morphological analysis to determine the roles of the promi nent myelin lipids galactocerebroside (GalC) and sulfatide in both central and peripheral myelin formation, exploiting mutant mice incapable of synthe sizing these lipids. Our results demonstrate a significant increase in unco mpacted myelin sheaths, the frequency of multiple cytoplasmic loops, redund ant myelin profiles, and Schmidt-Lanterman incisures in the CNS of these mu tant mice. In contrast, PNS myelin appeared structurally normal in these an imals; however, at post-natal day 10, greater than 10% of the axons withere d and pulled away from their myelin sheaths. These results indicate that Ga lC and sulfatide are critical to the formation of CNS myelin. In contrast, PNS myelin formation is not dependent on these lipids; however, GalC and su lfatide appear to be instrumental in maintaining Schwann cell-axon contact during a specific developmental window.