Hepatic iron deposition does not predict extrahepatic iron loading in mouse models of hereditary hemochromatosis
Subramaniam, V.N., McDonald, C.J., Ostini, L., Lusby, P.E., Wockner, L.F., Ramm, G.A., & Wallace, D.F. (2012) Hepatic iron deposition does not predict extrahepatic iron loading in mouse models of hereditary hemochromatosis. The American Journal of Pathology, 181(4), pp. 1173-1179.
Hereditary hemochromatosis is characterized by tissue iron loading and associated organ damage. However, the phenotype can be highly variable. The relationship between iron loading of different organs and the temporal nature of its deposition is still not well understood. We examined the progression of tissue iron loading in three mouse models to advance our understanding of the natural history of iron deposition in hereditary hemochromatosis. Wild-type, Hfe-/-, Tfr2-/-, and Hfe-/-/Tfr2-/- mice were analyzed at 3, 5, 10, 26, and 52 weeks, respectively. Hepatic, splenic, cardiac, and pancreatic iron concentrations were determined. Expression of both iron-regulatory and fibrosis genes was determined by quantitative real-time PCR in livers and hearts of 52-week-old mice. In all models, hepatic iron increased rapidly, plateauing before 10 weeks at different levels, depending on the genotype. Iron deposition in the pancreas and heart occurred after maximal iron loading of the liver was reached and was most marked in the Hfe-/-/Tfr2-/- mice. Although a significant positive correlation was identified between pancreatic and cardiac iron in all models at 52 weeks, there was no correlation between hepatic and either pancreatic or cardiac iron. There is variability in the timing and extent of tissue iron loading within a genotype, suggesting that hepatic iron levels in hereditary hemochromatosis may not accurately predict the iron content of other organs. © 2012 American Society for Investigative Pathology.
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|Item Type:||Journal Article|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
|Deposited On:||14 Oct 2016 00:52|
|Last Modified:||17 Oct 2016 04:05|
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