Comparison between dietary and cenetic copper deficiency in mice: Copper-dependent anemia

Abstract

Copper deficiency was produced by feeding a low copper diet to mice and rats during gestation and lactation. The copper-deficient offspring were compared to Brindled mice, which exhibit copper-deficient characteristics due to a genetic defect within the X-chromosome. Weanling mice nursed by dams fed the low copper diet exhibit classical signs of copper deficiency previously reported in other species, including: anemia, hypoceruloplasminemia, depressed brain copper levels, and cytochrome oxidase activities. However, in comparison to weanling rats derived from dams given the same treatment, the mice show only a minimal growth deficit and marginal copper depletion of liver with normal cytochrome oxidase, activity. Younger 11-day-old copper-deficient male mice also develop anemia, have low tissue copper levels (liver and kidney) and exhibit decreased ceruloplasmin activity. However, unlike copper-deficient rats, these mice do not have a decrease in serum ferroxidase activity. Age-matched Brindled mice are not anemic, even though they have low serum ferroxidase activity. Similar to the dietary deficient mice, Brindled mice do have low ceruloplasmin activity and low liver copper levels. In an attempt to resolve this enigma, mouse serum was chromatographed on Sephadex G-150. Only one ferroxidase activity peak, clearly separated from ceruloplasmin, was observed. Human and rat sera display two ferroxidase activity peaks, one chromatographing with ceruloplasmin activity, which is sensitive to azide, and a second peak which, like the mouse serum peak, appears as a shoulder on the void volume. These results demonstrate the potential of this mouse model in elucidating the nature of copper-dependent anemia. Furthermore, the data from this model suggest that changes in serum ferroxidase activity cannot explain the existence of anemia in dietary copper deficiency nor absence of anemia in genetic copper deficiency (Brindled mice).