Comparison of Copper Metabolism between Brindled Mice and Dietary Copper-Deficient Mice Using 67Cu

Abstract

Studies with 67Cu were conducted in suckling mice to differentiate between abnormal copper metabolism due to inadequate copper levels and that due to genetic factors. Brindled (Mobr/y) mice were compared to their normal brothers (Mo+/y) as well as to suckling mice that were copper-deficient (-Cu) because their dams were consuming a copper-deficient diet and a fourth group of suckling mice that served as dietary controls (+Cu). Male mice were injected with 67Cu when 8 days of age and were killed 3 days later. Whole-tissue 67Cu analysis revealed major labeling differences between the four groups, although the response in +Cu and Mo+/y animals was similar. Of seven tissues examined, liver accounted for the greatest percentage of 67Cu in +Cu (39%) and Mo+/y (39%) mice, and, to a lesser extent, in -Cu (7.6%) offspring, whereas kidney was highest for Mobr/y mice (10.5%). The labeling pattern for -Cu mice demonstrated an enrichment of 67Cu (counts per minute per milligram tissue) for all tissues with the exception of liver, compared to either +Cu or Mo+/y mice. Mobr/y mice showed an enrichment of 67Cu only kidney and bowel. Gel filtration chromatography was carried out on cytoplasmic extracts from liver, kidney and brain for all four groups. Three peaks were labeled: peak 1, void volume; peak 2, Ve:Vo = 1.59; peak 3, Ve:Vo = 2.24, where Ve is peak elution volume and Vo is void volume. Liver, kidney and brain cytosol of -Cu mice showed that more 67Cu was associated with a functional copper pool (peak 2, superoxide dismutase) rather than a storage pool (peak 3, metallothionein) compared to cytosol from +Cu or Mo+/y mice. In Mobr/y mice, more 67Cu was found with peak 3 than with peak 2, even in liver and brain, which are tissues that are low in total copper. Data indicate that the metabolism of copper in Mobr/y mice is different from -Cu mice.