The glycolipid composition of the spinal cord, sciatic nerve, kidney, liver and lung of twitcher mice, neurological mutants caused by a genetic deficiency of galactosylceramidase activity, was analyzed during development. No abnormal increase of galactosylceramide or sulfatide was detected in the spinal cord and the sciatic nerve at any age. Galactosylceramide and sulfatide in the whole tissue were in fact decreased in the spinal cord toward later stages of the disease. These findings were qualitatively similar but quantitatively milder than those in the genetically and enzymatically equivalent human disease, globoid cell leukodystrophy (Krabbe disease). Lactosylceramide was abnormally increased in both the spinal cord and the sciatic nerve, but glucosylceramide was increased only in the sciatic nerve. In contrast, there was a massive accumulation of galactosylceramide in the systemic organs. The hydroxy-fatty acid-containing (HFA-) galactosylceramide was predominant in all organs. In the kidney at 42 days, HFA-galactosylceramide was 50-fold and the nonhydroxy-fatty acid-containing (NFA-) galactosylceramide 5-fold higher than the normal levels. Although the absolute amount of galactosylceramide in the liver and lung was much smaller, it was also increased greatly in the twitcher mouse. Lactosylceramide was slightly to moderately increased in the systemic organs but there was no abnormality in glucosylceramide. The analytical findings in the twitcher kidney were in sharp contrast to those in the human disease, in which no abnormal accumulation of galactosylceramide occurs. The abnormal accumulation of the substrate for the deficient enzyme is more consistent with the concept of ldquo;lysosomal storage diseaserdquo;. Even though the underlying genetic defect is the same, its consequences show clear species differences.
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