Abstract
Tay-Sachs disease (TSD) is a fatal, genetically determined disorder of sphingoglycolipid metabolism, associated with the absence of the lysosomal enzyme B-D-N-acetylhexosaminidase A (Hex A) (1). There is a massive accumulation of GM2 ganglioside, and its asialo derivative GA2 in cells of the central nervous system. A cell culture which reproduces these biochemical parameters would permit one to measure the effect of enzyme replacement therapy under controlled conditions that are not easily attainable in vivo. Although skin fibroblasts cultured from TSD patients lack Hex A, these cultured cells do not accumulate GM2 ganglioside (2). Since TSD is a neuronal lipid storage disease, and since fetal TSD brain has the characteristic glycolipid patterns found in infant TSD brain, a cell strain from fetal TSD cerebellum was established and the glycolipid patterns were evaluated by TLC and GLC (3). The cells were labelled with 14C-glucosamine in order to compare the metabolic activity of the gangliosides over an extended time period. The cells were also transformed with the oncogenic DNA SV-40 virus (4) since we wished to establish a permanent cell line for the study of this disease.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Okada, S., and O’Brien, J. S., Tay-Sachs disease: Generalized absence of a Beta-D-N-Acetylhexosaminidase component, Science 165 (1969) 698–700.
Dawson, G., Matalon, R., and Dorfman, A., Glycosphingolipids in cultured human fibroblasts. II. Characterization and metabolism in fibroblasts from patients with errors of glycosphingolipid and mucopolysaccharide metabolism. J. Biol. Chem., 247 (1972) 5951–5958.
Hoffman, L. M., Amsterdam, D., and Schneck, L., GM2 ganglioside in fetal Tay-Sachs disease brain cell culture: A model system for the disease. Brain Res. (1975) In press.
Shein, H. M., Transformation of astrocytes and destruction of spongioblasts induced by Simian tumor virus (SV40) in cultures of human fetal neuroglia, J. Neuropath. & Exp. Neurol. 26 (1967) 60–76.
Amsterdam, D., and Brooks, S. E., Methodology: Cell culture. In B. W. Volk and L. Schneck (Eds.), The Gangliosidoses, Plenum Press, New York, 1975, pp. 265–270.
Suzuki, K., The pattern of mammalian brain gangliosides. II. Evaluation of the extraction procedures, post-mortem changes and the effect of formalin preservation, J. Neurochem. 12 (1965) 629–638.
Folch, J., Lees, M., and Sloane-Stanley, G. H., A simple method for the isolation and purification of total lipides from animal tissues, J. Biol. Chem., 226 (1957) 497–509.
Schneck, L., Pihkett, B., and Volk, B. W., Asialo GM2-gan-glioside in fetal Tay-Sachs disease brain, J. Neurochem. 24 (1975) 183–184.
Sandhoff, K., The hydrolysis of Tay-Sachs ganglioside (TSG) by human N-acetyl-B-D-hexosaminidase A, FEBS Lett. 11 (1970) 342–344.
Wenger, D. A., Okada, S., and O’Brien, J. S., Studies on the substrate specificity of hexosaminidase A and B from liver, Arch. Biochem. Biophys. 153 (1972) 116–129.
Greenbaum, M., Hoffman, L. M., and Schneck, L., Unpublished observations.
Sandhoff, K., Harzer, K., Wassle, W., and Jatzkewitz, H., Enzyme alterations and lipid storage in three variants of Tay-Sachs disease, J. Neurochem. 18 (1971) 2469–2489.
Navon, R., Padeh, B. and Adam, A., Apparent deficiency of hexosaminidase A in healthy members of a family with Tay-Sachs disease, Am. J. Hum. Genet. 25 (1973) 287–293.
Yanier, M. T., Holm, M., Mansson, J. E., and Svennerholm, L., Gangliosides of infant brain, J. Neurochem. 21 (1973) 1375–1384.
Robert, J., Freysz, L., Sensenbrenner, M., Mandel, P., and Rebel, G., Gangliosides of glial cells: A comparative study of normal astroblasts in tissue culture and glial cells isolated on sucrose-ficoll gradients, FEBS Lett. 50 (1975) 144–146.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1976 Plenum Press, New York
About this chapter
Cite this chapter
Schneck, L., Hoffman, L.M., Amsterdam, D., Brooks, S., Pinkett, B. (1976). Glycolipids in Cultured Fetal Tay-Sachs Disease Cerebellar Cells. In: Volk, B.W., Schneck, L. (eds) Current Trends in Sphingolipidoses and Allied Disorders. Advances in Experimental Medicine and Biology, vol 68. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7735-1_32
Download citation
DOI: https://doi.org/10.1007/978-1-4684-7735-1_32
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-7737-5
Online ISBN: 978-1-4684-7735-1
eBook Packages: Springer Book Archive