Brain lipids of a myelin-deficient rabbit mutant during development

The paralytic tremor (pt) rabbit, a neurological mutant, exhibits hypomyelination transmitted in X-linked recessive fashion. This rabbit mutant was used for regional lipid analyses of different brain structures during development. There was a significant decrease of myelin-specific lipids, particularly in the cerebroside and sulfatide in pt rabbits. The decrease of phospholipid and cholesterol was relevant to the total lipids depletion. The molar ratio of galactolipid to phospholipid decreased in the pt rabbit brain in each age group examined. The other lipids typical for myelin, such as ethanolamine glycerophospholipids, sphingomyelin, and GM1 ganglioside, were also diminished in the myelin-rich structures, but were not changed in the cortical gray matter of pt rabbits. In contrast, the total amount of gangliosides was near control levels and, therefore, in the mutant rabbits, the white matter and brain stem contained a higher proportion of lipid, as ganglioside, relative to the control animals. This result suggests that neuronal membranes were not involved in this pathology. The characteristic biochemical abnormalities exhibited in the pt rabbit suggest that a defect of oligodendroglial cell function is primarily responsible for the myelin abnormality.