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Zinc and Copper in Milk and Tissues of Nursing Lethal Milk Mutant Mice

John E. Piletz¹, Bo Lönnerdal, Lucille S. Hurley, Wade Berry^*, Roger E. Ganschow and Harvey R. Herschman^*

^* Laboratory of Biomedical and Environmental Sciences, University of California, Los Angeles, 90024, Department of Nutrition, University of California, Davis, CA 95616 and Institute of Developmental Research, Children's Hospital Research Foundation, Cincinnati, OH 45229

Zinc concentration was lower in liver of suckling 1-d-old lethal milk (lm/lm) mutant mice than in wild-type pups, in accordance with the hypothesis of milk-induced zinc deficiency previously proposed to underlie this mutation. Despite the initial deficiency, by 3 d of age suckling lm/lm pups exhibited higher levels of hepatic zinc than did lm/lm-nursed wild-type pups. Intestinal zinc and copper concentrations were normal in 1-d-old lm/lm pups, but by 3 d of age were also higher in lm/lm pups than in wild-type pups foster-nursed on lm/lm dams. Contrary to a previous report, we found that zinc concentration in milk of lm/lm dams was not significantly different from those of controls, between 4–20 d postpartum. Mutant milk showed 1) normal zinc distribution as determined by gel-filtration chromatography or by DEAE-cellulose chromatography of zinc-binding ligands derived from EDTA-dissociated micelles, 2) normal copper levels, 3) normal amounts of citrate, a zinc (II) and copper (II)-binding ligand and 4) normal amounts of glutamate, a proposed copper (II)-binding ligand. Total mammary glands and mammary gland cytosols from lm/lm mice exhibited normal zinc concentrations. Copper levels, however, were higher in lm/lm mammary gland cytosols than in controls. These results suggest that an increased uptake and/or retention of zinc and copper in the tissues studied may underlie the signs of zinc deficiency seen in lethal milk mutant mice.

KEY WORDS: • zinc • copper • acrodermatitis enteropathica • lethal milk

¹ To whom correspondence should be addressed: Cleveland Metropolitan General Hospital and Case Western Reserve University, Department of Psychiatry, 3395 Scranton Road, Cleveland OH 44109.

Manuscript received 4 September 1985. Revision accepted 21 August 1986.

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