Abstract
The enzymatic basis for the differences in hepatic ganglioside patterns in the mouse strains C57Bl/6 and Swiss White (SW) was investigated. SW has a “Swiss-type” ganglioside profile, expressing GM1 − and GD1a − in addition to GM2 − as major hepatic gangliosides, whereas C57Bl/6 shows a “GM2-type” profile, expressing only GM2 − as the major hepatic ganglioside. The enzyme UDP-galactose:GM2 ganglioside galactosyltransferase (GM2-GalT), which catalyzes the synthesis of GM1 ganglioside, showed a four- to fivefold elevation in intact and solubilized liver Golgi membrane fractions of the SW strain compared to C57Bl/6. Crosses between C57Bl/6 and SW produced an F1 generation with a hepatic ganglioside and enzymatic phenotype intermediate between those of the two parental strains. All three genotypic groups show two forms of the Golgi apparatus enzyme with isoelectric points of 6.5–6.8 and 8.3–9.0. The simplest mode of action of genes which control the enzymatic phenotype that would be consistent with these findings are one or two structural genes or one or two cis-regulatory genes affecting the rate of enzyme synthesis.
Similar content being viewed by others
References
Croze, E. M., and Morré, D. J. (1984). Isolation of plasma membrane, Golgi apparatus and endoplasmic reticulum fractions from single homogenates of mouse liver.J. Cell. Physiol. 11946.
Fishman, P. H., and Brady, R. O. (1976). Biosynthesis and function of gangliosides.Science 194906.
Fishman, P. H., Simmons, T. L., Brady, R. O., and Freese, E. (1974). Induction of glycolipid biosynthesis by sodium butyrate in HeLa cells.Biochem. Biophys. Res. Comm. 59292.
Ghidoni, R., Sonino, S., Chigorno, V., Venerando, B., and Tettamanti, G. (1983). Differences in liver ganglioside patterns in various inbred strains of mice.Biochem. J. 209885.
Hakomori, S. (1981). Glycosphingolipids in cellular interaction, differentiation and oncogenesis.Annu. Rev. Biochem. 50733.
Hashimoto, Y., Otsuka, H., Sudo, K., Suzuki, K., Suzuki, A., and Yamakawa, T. (1983a). Genetic regulation of GM2 expression in liver of mouse.J. Biochem. 93895.
Hashimoto, Y., Suzuki, A., Yamakawa, T., Miyashita, N., and Moriwaki, K. (1983b). Expression of GM1 and GD1a in mouse liver is linked to the H-2 complex on chromosome 17.J. Biochem. 942043.
Hashimoto, Y., Abe, M., Kiuchi, Y., Suzuki, A., and Yamakawa, T. (1984). Genetically regulated expression of UDP-N-acetylgalactosamine:GM3 (NeuGc):N-acetylgalactosaminyltransferase activity in mouse liver.J. Biochem. 951543.
Hashimoto, Y., Abe, M., Suzuki, A., Iwasaki, K., and Yamakawa, T. (1985). A locus controlling the activity of UDP-galactose:GM2 (NeuGc) galactosyltransferase in mouse liver is linked to the H-2 complex.Glycoconjugate J. 2255.
Holmgren, J., Elwing, H., Fredman, P., Strannegard, O., and Svennerholm, L. (1980). Gangliosides as receptors for bacterial toxins and Sendai virus.Adv. Exp. Med. Biol. 125453.
Kaplan, F., and Hechtman, P. (1983). Purification and properties of two enzymes catalyzing galactose transfer to GM2 ganglioside from rat liver Golgi.J. Biol. Chem. 258770.
Kaplan, F., and Hechtman, P. (1984). Rat liver Golgi galactosyltransferases: Distinct enzymes for glycolipid and glycoprotein acceptor substrates.Biochem. J. 217353.
Keenan, T. W., Morré, D. J., and Basu, S. (1974). Ganglioside biosynthesis: Concentration of glycosphingolipid glycosyltransferases in Golgi apparatus from rat liver.J. Biol. Chem. 249310.
Klenk, E. (1942). Uber die ganglioside, ein neue gruppe von zukerhaltigen gehirn lipoiden.Hoppe-Seyler Z. Physiol. Chem. 26876.
Leaback, D. H., and Walker, P. G. (1961). The fluorometric assay of N-acetyl-β-glucosaminidase.Biochem. J. 78151.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951). Protein measurement with folin-phenol reagent.J. Biol. Chem. 193265.
Markwell, M. K., Fredman, P., and Svennerholm, L. (1984). Specific gangliosides are receptors for Sendai virus.Adv. Exp. Med. Biol. 174369.
Partington, C. R., and Daly, J. W. (1979). Effect of gangliosides on adenylate cyclase activity in rat cerebral cortical membranes.Mol. Pharmacol. 15484.
Pinsky, L., Miller, J., Shanfield, B., Watters, G., and Wolfe, L. S. (1974). GM1 gangliosidosis in skin fibroblast culture: Enzymatic differences between types 1 and 2 and observations on a third variant.Am. J. Hum. Genet. 26563.
Roseman, S. (1970). The synthesis of complex carbohydrates by multiglycosyl-transferase systems and their potential function in intercellular adhesion.Chem. Phys. Lipids 5270.
Suzuki, A., Hashimoto, Y., Abe, M., Kiuchi, Y., and Yamakawa, T. (1984). Genetic regulation of GM2 (NeuGc) expression in liver of mouse.Adv. Exp. Med. Biol. 174407.
Suzuki, M., Nakamura, K., Hashimoto, Y., Suzuki, A., and Yamakawa, T. (1986). Mouse liver gangliosides.Carbo. Res. 151213.
Svennerholm, L. (1957). Quantitative estimation of sialic acids II. A colorimetric resorcinol-HCl method.Biochim. Biophys. Acta 24604.
Svennerholm, L. (1963). Chromatography of Human Brain Gangliosides.J. Neurochem. 10613.
Vengris, V. E., Fernie, B. F., and Pitha, P. M. (1980). The interaction between gangliosides and interferon.Adv. Exp. Med. Biol. 125479.
Wolfe, L. S. (1972). Methods for the separation and determination of gangliosides. In Marks, N., and Rodnight, R. (eds.),Research Methods in Neurochemistry Plenum, New York, pp. 232–248.
Author information
Authors and Affiliations
Additional information
This work was supported by a grant from the Medical Research Council (Canada) to its Human Genetics Research Group. D.S. thanks the MRC and the McGill University faculty of medicine for studentship support.
Rights and permissions
About this article
Cite this article
Sokoloff, D., Hechtman, P. Genetic control of ganglioside biosynthesis in mice. Biochem Genet 26, 631–644 (1988). https://doi.org/10.1007/PL00020502
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/PL00020502