Long‐term sequelae of HFE deletion in C57BL/6 × 129/O1a mice, an animal model for hereditary haemochromatosis

Publisher Website
Google Scholar
Abstract
Background HFE knockout mice (C57BL/6 × 129/Ola strain) mimic the functional aberrations of human hereditary haemochromatosis (HH) in short‐term experiments. The present study investigates functional and morphological long‐term changes.MethodsHFEo/o, HFE+/oand HFE+/+mice were maintained on iron‐rich and control diets for 2 weeks, 3, 12 and 18 months. Light microscopic tissue iron distribution, pathomorphological alterations, tissue iron content and oxidative stress were analysed in liver, pancreas, spleen, gastrointestinal tract, kidneys and myocardium. Additionally, duodenal59Fe absorption and59Fe whole body loss were measured.ResultsIron distribution between organs and microscopic iron deposition in the tissues resembled the patterns described in HH. After 3 months of iron‐rich feeding duodenal59Fe absorption decreased to ∼15% of iron‐adequate controls but remained about twice as high in HFEo/oas in HFE+/+mice. Hepatic iron concentrations reached only half the values known to induce hepatic fibrosis in rats and humans, while whole body59Fe loss was about twice as high. Consequently no hepatic fibrosis developed, although massive hepatocellular iron deposition and indication for oxidative stress were observed.ConclusionC57BL/6 × 129/O1a HFEo/omice mimic HH iron distribution and the regulation of intestinal iron absorption after long‐term feeding. However, characteristic morphological late changes in untreated HH are not modelled.