Glycolipids in Cultured Fetal Tay-Sachs Disease Cerebellar Cells
- 57 Downloads
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.
KeywordsEnzyme Replacement Therapy Fetal Brain Hydroxy Fatty Acid Infant Brain Cerebellar Cell
Unable to display preview. Download preview PDF.
- 3.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.Google Scholar
- 5.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.Google Scholar
- 11.Greenbaum, M., Hoffman, L. M., and Schneck, L., Unpublished observations.Google Scholar