Abstract
Adult lethal milk (lm/lm) mutant mice display increased induction of hepatic metallothionein synthesis compared to wild-type mice following the subcutaneous injection of 40 µmol ZnCl2/kg mouse. At this zinc dose the rate of incorporation of |35S| cysteine into hepatic metallothionein in adult (100-to 230-day-old) lm/lm mice was approximately 2.4-fold greater than the rate of incorporation of isotope in wild-type animals. At a higher zinc dose (160 µmol ZnCl2/kg) the incorporation of |35S| cysteine into hepatic metallothionein was similar in lm/lm and wild-type mice. The altered dose-response to zinc administration was not due to a change in hepatic zinc, copper, or manganese levels, to a difference in 65Zn uptake, or to an alteration in 65Zn bound to differential centrifugation fractions of adult lm/lm liver. 65Zn bound to hepatic metallothionein was, however, increased in aging lm/lm mice with symptomatic skin lesions.
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Aggett, P. J., Atherton, D. J., More, J., Davey, J., Delves, H. T., and Harries, J. T. (1980). Symptomatic zinc deficiency in a breast-fed preterm infant. Arch. Dis. Child. 55547.
Andersen, R. D., Winter, W. P., Maher, J. J., and Bernstein, I. A. (1978). Turnover of metallothioneins in rat liver. Biochem. J. 174327.
Bakka, A., and Webb, M. (1981). Metabolism of zinc and copper in the neonate: Changes in the concentrations and contents of thionein-bound Zn and Cu with age in the livers of the newborn of various mammalian species. Biochem. Pharmacol. 30721.
Bazzell, K. L., Coleman, R. L., and Nordquist, R. E. (1979). Induction of metallothionein-like protein in human breast tumor cells. Toxicol. Appl. Pharmacol. 50199.
Beach, R. S., Gershwin, M. E., and Hurley, L. S. (1980). Growth and development in postnatally zinc-deprived mice. J. Nutr. 110201.
Cousins, R. J. (1979). Regulatory aspects of zinc metabolism in liver and intestine. Nutr. Rev. 3797.
Davis, B. J. (1964). Disc electrophoresis. II. Method and application to human serum proteins. Ann. N.Y. Acad. Sci. 121404.
Erway, L., Hurley, L. S., and Fraser, H. S. (1970). Congenital ataxia and otolith defects due to manganese deficiency in mice. J. Nutr. 100643.
Erway, L. C., Piletz, J. E., and Ganschow, R. E. (1979). Other effects associated with the lethal milk mutation. Mouse Newslett. 6042.
Etzel, K. R., Shapiro, S. G., and Cousins, R. J. (1979). Regulation of liver metallothionein and plasma zinc by the glucocorticoid dexamethasone. Biochem. Biophys. Res. Comm. 891120.
Grider, A., Jr., and Erway, L. C. (1982). Metallothionein, zinc, and otoliths in lethal milk. Mouse Newslett. 6656.
Hogeboom, G. H. (1955). Fractionation of cell components in animal tissues. In Colowick, S. P., and Kaplan, N. O. (eds.), Methods in Enzymology, Vol. 1 Academic Press, New York, p. 16.
Johnson, P. E., and Evans, G. W. (1980). Sources of maternal milk zinc for absorption by suckling rats. Proc. Soc. Exp. Biol. Med. 163372.
Karin, M., and Herschman, H. R. (1979). Dexamethasone stimulation of metallothionein synthesis in HeLa cell cultures. Science 204176.
Karin, M., and Herschman, H. R. (1980). Glucocorticoid hormone receptor mediated induction of metallothionein synthesis in HeLa cells. J. Cell. Physiol. 10335.
Karin, M., Herschman, H. R., and Weinstein, D. (1980). Primary induction of metallothionein by dexamethasone in cultured rat hepatocytes. Biochem. Biophys. Res. Comm. 921052.
Keen, C. L., and Hurley, L. S. (1980). Developmental changes in concentrations of iron, copper, and zinc in mouse tissues. Mech. Age. Dev. 13161.
Laskey, R. A., and Mills, A. D. (1975). Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. Eur. J. Biochem. 56335.
Mutch, P. B., and Hurley, L. S. (1974). Effect of zinc deficiency during lactation on postnatal growth and development in rats. J. Natur. 104828.
Neldner, K. H., and Hambidge, K. M. (1975). Zinc therapy of acrodermatitis enteropathica. N. Engl. J. Med. 292879.
Olafson, R. W. (1981). Differential pulse polarographic determination of murine metallothionein induction kinetics. J. Biol. Chem. 2561263.
Piletz, J. E., and Ganschow, R. E. (1978). Zinc deficiency in murine milk underlies expression of the lethal milk (lm) mutation. Science 199181.
Piletz, J. E., and Ganschow, R. E. (1979). Lethal milk mutation results in dietary zinc deficiency in nursing mice. Am. J. Clin. Nutr. 31560.
Purichia, N., and Erway, L. C. (1972). Effects of dichlorophenamide, zinc, and manganese on otolith development in mice. Dev. Biol. 27395.
Richards, M. P., and Cousins, R. J. (1975). Influence of parenteral zinc and actinomycin D on tissue zinc uptake and the synthesis of a zinc-binding protein. Bioinorg. Chem. 4215.
Rudd, C. J., and Herschman, H. R. (1978). Metallothionein accumulation in response to cadmium in clonal rat liver cell line. Toxicol. Appl. Pharmacol. 44511.
Ryden, L., and Deutsch, H. R. (1978). Preparation and properties of the major copper-binding component in human fetal liver. J. Biol. Chem. 253519.
Wong, K.-L., and Klaassen, C. D. (1979). Isolation and characterization of metallothionein which is highly concentrated in newborn rat liver. J. Biol. Chem. 25412399.
Zimmerman, A. W., Hambidge, K. M., Lepow, M. L., Greenberg, R. D., Stover, M. L., and Casey, C. E. (1982). Acrodermatitis in breast-fed premature infants: Evidence for a defect of mammary zinc secretion. Pediatrics 69176.
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This work was supported by Contract DE AM03 76 SF00012 between the Department of Energy and the Regents of the University of California. JEP is the recipient of a National Research Service Award from the National Institutes of Health.
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Piletz, J.E., Herschman, H.R. Induction of metallothionein by zinc in lethal milk mutant mice. Biochem Genet 20, 1221–1233 (1982). https://doi.org/10.1007/BF00498945
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DOI: https://doi.org/10.1007/BF00498945