Abstract
Cultured cells of a variety of different types from human Menkes' syndrome patients and brindled mouse mutants exhibit similarly altered responses to changes in extracellular copper concentration. This suggests that the mutations in the mouse and human are very similar and that mutant gene expression is occurring in many different tissues. Intracellular copper levels are markedly elevated in mutant cells in normal medium and in medium containing a hundredfold higher copper. Some cell lines from heterozygotes possess elevated copper levels. Elevated extracellular copper and zinc are significantly more toxic to mutant cells. Mutant cells exhibit normal rates of uptake of copper-64 over a 10-min period but abnormally high accumulation over 24 hr and low rates of efflux. Menkes' fibroblasts become saturated with copper-64 at lower extracellular concentrations than for normal fibroblasts. These data support the idea of enhanced intracellular binding in mutant cells.
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References
Beratis, N. G., Price, P., LaBadie, G., and Hirschhorn, K. (1978). 64Cu metabolism in Menkes and normal cultured skin fibroblasts. Pediat. Res. 12699.
Camakaris, J., Danks, D. M., and Borger, P. (1976). Studies of copper metabolism in Menkes' syndrome. Aust. Paediat. J. 12222.
Chan, W., Garnica, A. D., and Rennert, O. M. (1978). Cell culture studies of Menkes kinky hair disease. Clin. Chim. Acta 88495.
Danks, D. M. (1975). Steely hair, mottled mice, and copper metabolism. New Engl. J. Med. 2951147.
Danks, D.M. (1977). Copper transport and utilisation in Menkes' syndrome and in mottled mice. Inorg. Perspect. Biol. Med. 173.
Danks, D. M., Campbell, P. E., Walker-Smith, J., Stevens, B. J., Gillespie, J. M., Blomfield, J., and Turner, B. (1972). Menkes' kinky-hair syndrome. Lancet 11100.
Danks, D. M., Cartwright, E., Stevens, B. J., and Townley, R. R. W. (1973). Menkes' kinky hair disease: Further definition of the defect in copper transport. Science 1791140.
Goka, T.J., Stevenson, R.E., Hefferan, P. M., and Howell, R. R. (1976). Menkes' disease: A biochemical abnormality in cultured human fibroblasts. Proc. Natl. Acad. Sci. 73604.
Horn, N. (1976). Copper incorporation studies on cultured cells for prenatal diagnosis of Menkes' disease. Lancet 11156.
Hunt, D. (1974). Primary defect in copper transport underlies mottled mutants in the mouse. Nature 249852.
Mann, J. R., Camakaris, J., and Danks, D. M. (1979). Copper metabolism in mottled mouse mutants. Distribution of 64Cu in brindled (Mobr) mice. Biochem. J. 180613.
Paul, J. (1975). In Cell and Tissue Culture 5th ed. Churchill Livingstone, Edinburgh, p. 226.
Volpintesta, E. J. (1974). Menkes' kinky hair syndrome in a black infant. Am. J. Dis. Child. 128244.
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This work was supported by grants from the Australian National Health and Medical Research Council, the McPherson/Shutt Trust, and the Apex Foundation.
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Camakaris, J., Danks, D.M., Ackland, L. et al. Altered copper metabolism in cultured cells from human Menkes' syndrome and mottled mouse mutants. Biochem Genet 18, 117–131 (1980). https://doi.org/10.1007/BF00504364
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DOI: https://doi.org/10.1007/BF00504364