Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux

• DOI: 10.1073/pnas.96.19.10812
• Publication Date: 2002-07-26T14:35:07Z
• Authors: Z. Leah Harris; Alison P. Durley; Tsz Kwong Man; Jonathan D. Gitlin
• Keywords: Ceruloplasmin; Mononuclear phagocyte system; Ferroportin; Parenchyma

Aceruloplasminemia is an autosomal recessive disorder of iron metabolism. Affected individuals evidence accumulation in tissue parenchyma association with absent serum ceruloplasmin. Genetic studies such patients reveal inherited mutations the ceruloplasmin gene. To elucidate role homeostasis, we created animal model aceruloplasminemia by disrupting murine ( Cp ) Although normal at birth, −/− mice demonstrate progressive that one year age all animals have a prominent elevation ferritin and 3- to 6-fold increase content liver spleen. Histological analysis affected tissues these shows abundant stores within reticuloendothelial cells hepatocytes. Ferrokinetic +/+ equivalent rates absorption plasma turnover, suggesting results from altered compartmentalization cycle. Consistent this concept, showed no abnormalities cellular uptake but striking impairment movement out Our findings essential physiologic for determining rate efflux mobilizable stores.