Alterations in serum and tissue iron profiles associated with mutations in the fitness1^4226SB Locus of mice

We investigated alterations in serum and tissue iron profiles that were associated with an N-ethylN-nitrosourea-induced mutation in the fitness I locus in chromosome 7 in mice. Mice hemizygous for the fitness 1 mutation [c fitness1^4226SB/Df(c Mod2 shl)^26DVT] had a microcytic, hypochromic anaemia which was associated with a lower concentration of iron in the serum compared to age-matched, control mice [c^ch+/c^ch+]. The hemizygous mutants had a greater total iron binding capacity and an increased unsaturated iron binding capacity compared to controls. The percentage transferrin saturation was significantly decreased in the hemizygous mutant mice compared to control mice. The concentration of iron within several body organs was determined and hemizygous mutant mice had a greater concentration of iron in the liver compared to controls. In contrast, the mutants had a lower concentration of iron within the spleen, kidneys and heart compared to control mice. Microscopic analysis of bone marrow smears indicated less iron in the smears from the hemizygous mutants. From these data, it was concluded that the fitness1^4226SB mutation in mice causes alterations in the serum iron profile that resemble iron deficiency. The alterations in tissue iron concentrations indicate an abnormal distribution or mobilisation of iron between organ systems. The exact mechanism(s) by which the fitness1^4226SB mutation mediates these abnormalities in iron distribution remains to be determined.