Copper deficient rats and mice both develop anemia but only rats have lower plasma and brain iron levels

Abstract

Iron homeostasis depends on adequate dietary copper but the mechanisms are unknown. Mice (Mus musculus) and rat (Rattus norvegicus) offspring were compared to determine the effect of dietary copper deficiency (Cu-) on iron status of plasma, liver, brain and intestine. Holtzman rat and Hsd:ICR (CD-1) outbred albino mouse dams were fed a Cu- diet and drank deionized water or Cu supplemented water. Offspring were sampled at time points between postnatal ages 13 and 32. Cu- rat and mouse pups were both anemic, but only rat pups had lower plasma and brain iron levels. Plasma iron was lower throughout the suckling period in Cu- rats but not Cu- mice. Cu- mice derived from dams restricted of Cu only during lactation were also severely anemic without hypoferremia. Intestinal metal analysis confirmed that Cu- pups had major reductions in intestinal concentration of Cu, increased Fe, and normal Zn. However, whole mouse (less the intestine) analysis demonstrated normal content of Fe indicating that the limitation in iron transport by intestinal hephaestin had no consequence to total iron reserves of the mouse. Further research will be needed to determine the reason Cu- mice were anemic since the "ferroxidase" hypothesis does not explain this phenotype.

Fig. 1

Effect of Cu deficient treatment on hemoglobin (A) and brain iron (B) concentrations in Cu+ and Cu- P27-26 weanling mice and rats. Each bar represents the mean ± SEM (n=3–6). * Indicates a significant difference from Cu+, P < 0.05 (Student’s t-test).

Fig. 2

Effect of Cu deficient treatment during development on plasma iron concentrations in Cu+ and Cu- rats (A) and mice (B). Treatment began at E7 for rats and E17 for mice. Each bar represents means ± SEM (n=3–5). * Indicates a significant difference from Cu+, P < 0.05 (Student’s t-test).

Fig. 3

Effects of Cu deficient treatment during lactation plus postweaning on mouse hemoglobin (A), plasma iron (B), and brain iron (C) concentrations in P27 mice. Each bar represents means ± SEM (n=5–6). * Indicates a significant difference from Cu+, P < 0.05 (Student’s t-test).

Fig. 4

Effects of Cu deficient treatment during lactation plus postweaning on intestinal content and concentrations of copper (A,B), iron (C,D), and zinc (E,F) in Cu+ and Cu- P32 mice. Each bar represents means ± SEM (n=4). * Indicates a significant difference from Cu+, P < 0.05 (Student’s t-test).

Fig. 5

Effects of Cu deficient treatment during lactation plus postweaning on whole mouse (less the intestine) content and concentrations of copper (A,B), iron (C,D), and zinc (E,F) in Cu+ and Cu- P32 mice. Each bar represents means ± SEM (n=4). * Indicates a significant difference from Cu+, P < 0.05 (Student’s t-test).