Nuclear iron deposits in hepatocytes of iron-loaded HFE-knock-out mice: a morphometric and immunocytochemical analysis

Nuclear deposits of stainable iron in hepatocytes are a sign of liver iron overload in mice. Animals with no, partial or total knock-out of the HFE alleles, the deletion of which is responsible for hereditary haemochromatosis, were given different forms of dietary iron to measure nuclear iron deposits which were then related to cytoplasmic iron load. Wild type and heterozygous HFE-knock-out mice kept for 52 weeks on a standard diet showed no such deposits. These were, however, demonstrated in low numbers and with small diameters in homozygous HFE-knock-out mice kept on this diet. Nuclear iron deposits were most abundant in all type of mice fed carbonyl iron (2.5% w/w) for 52 weeks almost irrespective of their genetic background. The diameter of these deposits increased with the genetically conditioned extent of hepatocellular iron overload. Mice that were fed a diet containing TMH-ferrocene for 4 weeks showed amounts of hepatic iron that were comparable to those in the carbonyl iron-fed group but nuclear deposits were small and present in only 0.3% of the hepatocytes. While surrounding karyoplasm was immunostained for H- and L-ferritin, the nuclear iron deposits were not. As the nuclear iron deposits corresponded electron microscopically to aggregated ferritin molecules, they represent a non-immunoreactive form of presumably denatured ferritin.