Repletion of copper-deficient mice and brindled mice with copper or iron

Studies were conducted in suckling mice to investigate copper-dependent anemia. Brindled (Mobr/y) mice, which have a genetic defect that affects copper metabolism, were compared to their normal brothers (Mo+/y) as well as to anemic suckling mice that were copper-deficient (-Cu) because their dams were consuming a diet low in copper and to a fourth group of control suckling mice (+Cu) from copper-supplemented dams. Mice were given a subcutaneous injection of NaCl, FeCl2 or CuCl2 providing 50 micrograms of Na, Fe or Cu, respectively, when 7 days old and were killed 5 days later. Injection of FeCl2 into -Cu mice elevated liver iron 2.7-fold and raised hemoglobin levels to those observed in the +Cu and Mo+/y mice. Ceruloplasmin activity remained low at 5% of control levels. Injection of CuCl2 into -Cu mice resulted in significant increases in body and brain weight, elevations in serum copper and ceruloplasmin activities and hemoglobin levels. Liver copper rose and iron fell, both to levels observed in +Cu and Mo+/y mice. Brain copper and norepinephrine concentrations rose to control levels. Injection of CuCl2 into Mobr/y mice, although resulting in darker pigmentation and normal serum copper and ceruloplasmin levels, failed to stimulate growth or change brain weight. Furthermore, liver and brain copper levels did not rise to normal levels despite significant improvements. Similarly, brain norepinephrine levels rose, but were still below normal. Brindled mice do not respond to copper therapy to the same degree as do -Cu mice. Iron therapy was successful in reversing the anemia of -Cu mice but was without effect on growth or brain development.