Mn transport into the brain is an important issue in Mn toxicity. The involvement of transferrin (Tf) in Mn transport is controversial. We propose the hypotransferrinemic mouse as a model for the study of the role of Tf in Mn transport. Mice heterozygotic for the hypotransferrinema mutation have 24% lower circulating Tf than wild-type mice. We hypothesized that Fe deficiency in these mice would provide a mouse model with normal to below normal Tf but decreased Tf saturation. Twenty-two weanling heterozygotic mice (Hh) and thirty-six wild-type BALB/c mice (HH) were fed diets containing either 0 or 35 mg/kg Fe, and killed at various time points from zero to eight weeks of dietary treatment. 24 h before killing, mice were injected ip with 1 μCi 54Mn. Plasma Tf (measured by immunoblot) in Hh mice decreased over the eight weeks in those fed the Fe-adequate diet. In Fe-deficient Hh mice, plasma Tf increased at 2 wk, then returned to baseline levels (67% of Fe-adequate HH). Plasma Fe in Hh mice fed the Fe-deficient diet was lower at each time point than in Fe-adquate Hh mice or in HH mice. Thus, Fe-deficient Hh mice had increased unsaturated Fe-binding capacity (UIBC). After 8 wk of dietary treatment, UIBC tended to correlate positively with 54Mn retention in spleen and heart, but negatively in brain and liver. These results suggest that Tf is not the most important delivery mechanism for Mn transport into the brain.
|Original language||English (US)|
|State||Published - Dec 1 1997|
All Science Journal Classification (ASJC) codes
- Molecular Biology