Transferrin response in normal and iron-deficient mice heterozygotic for hypotransferrinemia; effects on iron and manganese accumulation

Hypotransferrinemia is a genetic defect in mice resultingin 1% of normal plasma transferrin (Tf) concen-trations;heterozygotes for thismutation (+/hpx) have low circulating Tf concentrations. These mice providea unique opportunity toexamine the developmental pattern and response of Tf to iron-deficient diets, andfurthermore,to address the controversial role of Tf in Mn transport. Twenty-three weanling +/hpx miceandforty-five wild-type BALB/cJ mice were either killed at weaning or fed diets containing either13 or 72 mgkg Fe, and killed after four or eight weeks. Plasma Tfconcentrations were lower in +/hpx mice, plasmaTf nearly doubled and liver Tf was only 50% of normalin response to iron deficiency. Brain iron concen-trationdid not correlate significantlywith either plasma Tf or TIBC. However, iron accumulation into braincontinued with irondeficiency whereas most other organs had less iron. These results imply that eitherthereis a selected targeting of iron to the brain by plasma Tf or there is an alternative irondelivery system tothe brain. Furthermore, we observed no differences in tissuedistribution of Mn despite the differences incirculating Tf concentrationsand body iron stores; this suggests that there are non-Tf dependent mecha-nismsfor Mntransport.