Kinetics of Iron Import into Developing Mouse Organs Determined by a Pup-Swapping Method [Developmental Biology]

November 4th, 2014 by Chakrabarti, M., Barlas, M. N., McCormick, S. P., Lindahl, L. S., Lindahl, P. A.

The kinetics of dietary iron-import into various organs of mice were evaluated using a novel pup swapping approach. Newborn pups whose bodies primarily contained 56Fe or 57Fe were swapped at birth such that each nursed on milk containing the opposite isotope. A pup from each litter was euthanized weekly over a 7 wk period. Blood plasma was obtained and organs were isolated typically after flushing with Ringers buffer. 56Fe and 57Fe concentrations were determined for organs and plasma; organ volumes were also determined. Mossbauer spectra of equivalent 57Fe-enriched samples were used to quantify residual blood in organs; this fraction was excluded from later analysis. Rates of import into brain, spleen, heart and kidneys were highest during the first 2 wks of life. In contrast, half of the Fe in the newborn liver exited during that time and influx peaked later. Two mathematical models were developed to analyze the import kinetics. The only one that simulated the data adequately assumed that an Fe-containing species enters the plasma and converts into a second species, and that both are independently imported into organs. Consistent with this, liquid chromatography with an on-line ICP-MS detector revealed numerous Fe species in plasma besides transferrin. Model fitting required that the first species, assigned to non-transferrin-bound iron (NTBI), import faster into organs than the second, assigned to transferrin-bound-iron (TBI). NTBI rather than TBI appears to play the dominant role in importing Fe into organs during early development of healthy mice.