Mutations in hemojuvelin (HJV) cause severe
juvenile hemochromatosis, characterized by
iron loading of the heart, liver, and pancreas. Knockout (KO) mice lacking HJV (Hjv-/-) spontaneously load with
dietary iron and, therefore, present a model for hereditary
hemochromatosis (HH). In HH,
iron chelation may be considered in noncandidates for phlebotomy. We examined the effects of
deferasirox, an oral
chelator, in Hjv-/- mice. Hepatic, cardiac, splenic, and pancreatic
iron were determined by measuring elemental
iron and scoring histological sections. Heart and liver
iron levels were also determined repeatedly by quantitative R2* magnetic resonance imaging (MRI). The time course of
iron loading without intervention was followed from Week 8 of age (study start) to Week 20, when once-daily (5x/week)
deferasirox was administered, to Week 28. At 8 weeks, liver
iron of KO mice was already markedly elevated versus wild-type mice (P<0.001) and reached a plateau around Week 14. In contrast, Week 8 cardiac and pancreatic
iron levels were similar in both KO and wild-type mice and, compared with the liver, showed a delayed but massive
iron loading up to Week 20. Contrary to the liver, heart, and pancreas, the KO mice spleen had lower
iron content versus wild-type mice. In Hjv-/- mice, liver and heart
iron burden was effectively reduced with
deferasirox 100 mg/kg (P<0.05). Although
deferasirox was less efficacious at this dose in the pancreas, over the observed time period, a clear trend toward reduced organ
iron load was noted. There was no noticeable effect of
deferasirox upon splenic
iron in Hjv-/- mice. Quantitative R2* MRI demonstrated the ability to assess
iron concentrations in the liver and myocardial muscle accurately and repetitively. Hepatic (R=0.86; P=3.2*10(-12)) and delayed myocardial (R=0.81; P=2.9*10(-10))
iron accumulation could be followed noninvasively with high agreement to invasive methods.