Impaired Copper Homeostasis in Neonatal Male and Adult Female Brindled (Mobr) Mice

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Abstract
Copper metabolism was analyzed in Brindled (Mobr) male mice and in heterozygous Brindled (Mobr) adult female mice. The intestines of Mobr mice suckling dams injected with 64Cu contained 72% of the radioactivity absorbed from the mother's milk and the liver contained 64Cu was found in the liver of these pups. The copper concentration in the kidneys from Mobr males was significantly greater than the concentration of copper in the kidneys from normal pups. When Mobr 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 Mobr 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 Mobr 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 Mobr male mice. When either 1.0 µg or 10 µg of 64Cu was administered orally to adult female mice, the Mobr females absorbed approximately 30% less copper than the normal females. The rate of copper excretion was decreased in adult Mobr females and the kidney copper concentration of the Mobr was significantly greater than that of normal females. These results demonstrate that copper homeostasis is altered in both adult Mobr female mice and their neonatal Mobr male offspring.

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