Glycolipids in Cultured Fetal Tay-Sachs Disease Cerebellar Cells

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.