Neurological mutation characterized by dysmyelination in NCTR-Balb/C mouse with lysosomal lipid storage disease.
Morphological and biochemical studies were performed on the CNS of neurologically affected NCTR-Balb/C mouse. Histological and electron microscopic techniques demonstrated severe myelin deficiency in the affected brains. Neither the presence of lipid-containing macrophages nor reactive gliosis was apparent. Analysis of myelin-associated lipids and proteins revealed prominent depletion of galactocerebroside, sulfatide, and proteolipid proteins. In contrast to the scarcity of myelin-specific constituents a marked accumulation of GM2 and GM3 gangliosides and several neutral glycolipids, i.e., glucocerebroside, lactosylceramide, gangliotriaosylceramide, and gangliotetraosylceramide were found in affected CNS. These abnormalities were already apparent in 12-day-old pups as well as in 65-day-old mice. A significant deficit in the proportion of long-chain fatty acids (C24), notable in both normal and alpha-hydroxy acids of cerebrosides from affected white matter, was measured. The lack of reactive gliosis, the observed depletion of galactocerebroside and sulfatide at the early age of 12 days, and the relative decrease in long-chain fatty acids in affected CNS strongly suggest a defect in myelinogenesis in this mutant rather than a secondary process of myelin breakdown.
D000818:Animals; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D001923:Brain Chemistry; D002554:Cerebrosides / Q000032:analysis; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D005732:Gangliosides / Q000032:analysis; D006028:Glycosphingolipids / Q000032:analysis; D008052:Lipid Metabolism, Inborn Errors / Q000473:pathology*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000033:anatomy & histology* / Q000378:metabolism; D008854:Microscopy, Electron; D009185:Myelin Proteins / Q000032:analysis; D009186:Myelin Sheath / Q000473:pathology* / Q000648:ultrastructure; D011510:Proteolipids / Q000032:analysis
D002554:Cerebrosides; D005227:Fatty Acids; D005732:Gangliosides; D006028:Glycosphingolipids; D009185:Myelin Proteins; D011510:Proteolipids