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Impaired Copper Homeostasis in Neonatal Male and Adult Female Brindled (Mo^br) Mice

United States Department of Agriculture, Agricultural Research Service, Human Nutrition Laboratory, Grand Forks, North Dakota 58201

Copper metabolism was analyzed in Brindled (Mo^br) male mice and in heterozygous Brindled (Mo^br) adult female mice. The intestines of Mo^br mice suckling dams injected with ⁶⁴Cu contained 72% of the radioactivity absorbed from the mother's milk and the liver contained <3% of the label obtained via the milk. The intestines from normal pups suckling labeled dams never contained more than 25% of the label taken up from the milk and approximately 50% of the absorbed ⁶⁴Cu was found in the liver of these pups. The copper concentration in the kidneys from Mo^br males was significantly greater than the concentration of copper in the kidneys from normal pups. When Mo^br male pups and normal pups were given two injections of 10 µg Cu, approximately 2.6% of the injected copper was recovered in the liver of the Mo^br pups at autopsy but approximately 38% of the copper injected into the normal pups was present in the liver at autopsy. The copper injections produced a 3.5-fold increase in the kidney copper concentration of Mo^br mice but there was no significant increase in the copper content of the kidneys from normal mice. These results demonstrate that both intestinal copper absorption and hepatic copper uptake are impaired in Mo^br male mice. When either 1.0 µg or 10 µg of ⁶⁴Cu was administered orally to adult female mice, the Mo^br females absorbed approximately 30% less copper than the normal females. The rate of copper excretion was decreased in adult Mo^br females and the kidney copper concentration of the Mo^br was significantly greater than that of normal females. These results demonstrate that copper homeostasis is altered in both adult Mo^br female mice and their neonatal Mo^br male offspring.

KEY WORDS: • copper absorption • copper homeostasis • Menkes' steely-hair syndrome • Brindled mice

Manuscript received 1 August 1977.