Study of Pathogenesis in Twitcher Mouse, an Enzymatically Authentic Model of Human Krabbe’s Disease
Krabbe’s disease (globoid cell leukodystrophy; McKusick 24520) is a genetic neurological disorder due to an enzymic deficiency of galactosylceramidase. The disease is conceptually a lysosomal storage disorder but galactosylceramide (Galcer), the natural substrate of the deficient enzyme, apparently does not accumulate despite the genetic catabolic block (Suzuki and Suzuki, 1983). Recently, accumulation of galactosylsphingosine (Galsph) was demonstrated in nervous system in human Krabbe’s disease (Svennerholm et al., 1980) and its animal model (twitcher mouse) (Igisu and Suzuki, 1984). The Galsph, also a substrate of galactosylceramidase, has a cell toxicity which resulted in cell dysfunction. However, the reason why Galcer accumulation does not occur and how Galsph was made still remain unclear. To answer these questions, in vivo synthesis of Galcer and Galsph in a sciatic nerve culture and in vitro enzymic activities for synthesis of Galcer and Galsph in spinal cord were examined.
KeywordsSpinal Cord Sciatic Nerve Lipid Extract Normal Mouse Deficient Enzyme
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- Suzuki, K. and Suzuki, Y. Galactosylceramide lipidosis: Globoid cell leukodystrophy (Krabbe’s disease). In: Stanbury, J. B., Frederickson, D. S., Goldstein, J. L. and Brown, M. S. (eds.) The Metabolic Basis of Inherited Disease, McGraw-Hill, New York, 1983, pp. 857–880Google Scholar