Galactosylsphingosine in Murine and Human Tissues of Normal and Globoid Cell Leukodystrophy Cases
Globoid cell leukodystrophy (Krabbe’s disease, GLD) is a neurological dijogder of infancy caused by a genetic deficiency of galactosyl-ceramidase I.1,2 The murine analogue is twitcher mouse, in which galactosyl-ceramidase I is also deficient.3,4 The pathological features are similar to those of human GLD. In both, severe demyelination occurs in central and peripheral nervous tissues. In addition, gliosis, loss of oligodendrocytes, and presence of globoid cells are evident in the white matter. Galactosylceramide, a natural substrate of the deficient enzyme, apparently does not accumulate in the nervous tissues of human and murine cases of GLD. In 1972, Miyatake and Suzuki6 found that the hydrolysis of galactosylsphingosine (psychosine) is impaired in tissues from GLD patients and proposed, for the pathogenesis of GLD, the “psychosine hypothesis” which postulates that the degeneration of oligodendrocytes and consequent demyelination in the GLD tissue are due to the toxicity of galactosylsphingosine. In 1980, Svennerholm et al demonstrated an abnormal accumulation of galactosylsphingosine in the brains of GLD patients and supported the hypothesis. As to the twitcher mouse, Igisu and Suzuki8 noted an accumulation of the compound, determined by fluorometric assay using TLC. In this paper, we describe a procedure for the determination of galactosylsphingosine, using HPLC, and data on galactosylsphingosine content in tissues from normal and twitcher mice. The data on normal human tissues and tissues from a patient with GLD are also described.
KeywordsSpinal Cord Sciatic Nerve Nervous Tissue Normal Human Tissue Twitcher Mouse
Unable to display preview. Download preview PDF.
- 1.K. Suzuki, and Y. Suzuki, Galactosylceramide lipidosis: Globoid cell leukodystrophy (Krabbe’s disease), in: The Metabolic Basis of Inherited Disease, J. B. Stanbury, J. B. Wyngaarden, D. S. Fredrickson, J. L. Goldstein, and M. S. Brown, eds., 5th edition, McGraw-Hill, New York, pp. 857 (1983).Google Scholar
- 2.T. Kobayashi, N. Shinnoh, I. Goto, and Y. Kuroiwa, Hydrolysis of galactosylceramide is catalyzed by two genetically distinct acid (3-galactosidases, J. Biol. Chem. 260:14892 (1985).Google Scholar
- 4.T. Kobayashi, N. Shinnoh, and Y. Kuroiwa, Metabolism of galactosylceramide in the twitcher mouse, an animal model of human globoid cell leukodystrophy, Biochim. Biophys. Acta 879:215 (1986).Google Scholar
- 5.L. W. Duchen, E. M. Eicher, J. M. Jacobs, F. Scaravilli, and F. Teixeira, Hereditary leucodystrophy in the mouse. The new mutant twitcher, Brain 103:695 (1980).Google Scholar
- 7.L. Svennerholm, M.-T. Vanier, and J.-E. Mansson, Krabbe disease. A galactosylsphingosine (psychosine) lipidosis, J. Lipid Res. 21:53 (1980).Google Scholar
- 9.H. Shinoda, T. Kobayashi, M. Katayama, I. Goto, and H. Nagara, Accumulation of galactosylsphingosine (psychosine) in the twitcher mouse: Determination by HPLC, J. Neurochem. 49:92 (1987).Google Scholar
- 13.T. Kobayashi, H. Nagara, K. Suzuki, and K. Suzuki, The twitcher mouse: determination of genetic status by galactosylceramidase assays on clipped tail, Biochem. Med. 27:8 (1982).Google Scholar
- 14.T. Kobayashi, H. Shinoda, I. Goto, T. Yamanaka, and Y. Suzuki, Globoid cell leukodystrophy is a generalized galactosylsphingosine (psychosine storage disease, Biochem. Biophys. Res. Commun. 144:41 (1987).Google Scholar
- 15.T. Taketomi, and K. Nishimura, Physiologic activity of psychosine, Jpn J. Exp. Med. 34:255 (1964).Google Scholar
- 18.S. Neuenhofer, E. Conzelmann, G. Schwarzmgnn, H. Egge, and K. Sandhoff Occurrence of lysoganglioside lysoGM2 (II-Neu5Ac-gangliotriaosylsphingosine) in GM2 gangliosidosis brain, Biol. Chem. Hoppe-Seyler 367:241 (1986).Google Scholar