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Changes in Tissue Growth, Concentrations of Copper, Iron, Cytochrome Oxidase and Superoxide Dismutase Subsequent to Dietary or Genetic Copper Deficiency in Mice¹

Department of Biochemistry, School of Medicine, University of Minnesota, Duluth; Duluth, MN 55812

Experiments were conducted in suckling mice to investigate copper-dependent anemia. Brindled (Mo^br/y) mice, which are not anemic, 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 a fourth group of suckling mice that served as dietary controls (+Cu). Compared to +Cu and Mo^+/y mice, -Cu mice were smaller and exhibited cardiac hypertrophy and significant atrophy of lymphoid tissues (spleen and thymus). Mo^br/y mice were also small and demonstrated modest atrophy of both liver and spleen. Cu levels were decreased in all -Cu mouse tissues studied, whereas Fe levels tended to be unaltered. Mo^br/y mice also exhibited lower tissue Cu levels in soft tissues, except for kidney and small intestine; however, Cu levels in Mo^br/y mice were greater than in -Cu mice. Functional copper deficiency was demonstrated in -Cu tissues by decreases in cytochrome c oxidase (CO) and cuprozinc-superoxide dismutase (SOD). The magnitude of the change was tissue specific. Mo^br/y tissues, which were low in Cu, also exhibited decreased SOD and CO activity. However, the drop in Mo^br/y tissue was less than in -Cu tissue. This was most pronounced in bone marrow, where both CO and SOD were four times higher in Mo^br/y than in -Cu mice. Both Mo^br/y and -Cu mice had low serum ceruloplasmin activities. The presence of anemia in -Cu mice and the absence of anemia in Mo^br/y mice may result from a more severe copper-deficient state in erythropoietic tissues in -Cu mice rather than from differences in ceruloplasmin activity.

KEY WORDS: • copper deficiency • brindled mice • copper-dependent anemia • cytochrome c oxidase • superoxide dismutase • copper • iron

¹ This research was supported by Public Health Service Research Grant HD-15491 from the National Institutes of Health.

Manuscript received 28 March 1983.

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