(585.1) Establishing Dietary Iron Requirements for Mouse and Rat Models of Hereditary Hemochromatosis

Poster Board Number: E341

Jennifer Lee (University of Florida), Yang Yu (University of Florida), Regina DeLellis (University of Florida), Pearl Ebea (University of Florida), Sean Zhu (University of Florida), Rufus Theophilus (University of Florida), James Collins (University of Florida)

The established iron requirement for laboratory rodents is 35-50 ppm, but standard rodent chows contain up to 350 ppm iron. Excess dietary iron exacerbates iron accumulation in hepcidin (Hamp) knockout (KO) mice and rats, which model the iron-overload disorder hereditary hemochromatosis (HH) in humans. Establishing iron requirements is important to allow for proper experimental design when studying Hamp KOs since WT littermates are not iron-loaded (and thus not an appropriate control group for iron-loaded Hamp KOs). We hypothesized that Hamp KOs have iron requirements at least 50% below those of WT animals, given that intestinal iron absorption is inappropriately elevated (by 2-3-fold) in the KOs. In the present study, WT and Hamp KO mice and rats of both sexes were weaned onto one of four AIN-93G purified rodent diets, with the following iron concentrations (in ppm): 5-7 (low), 17-20 (low marginal), 24-27 (high marginal), or 45-49 (adequate). After 6 weeks on the diets, bioindicators of iron status were assessed, including blood hemoglobin content and hematocrit, serum ferritin and nonheme iron content, tissue nonheme iron concentration, and blood transferrin saturation. Outcomes showed that significant iron loading occurred in Hamp KO animals when fed the high-marginal and adequate iron diets, as indicated by higher serum ferritin and nonheme iron content, elevated hepatic iron levels and increased TSAT. Iron loading, however, did not occur when the KO rats and mice were fed the low-marginal iron diets. Animals fed the low-iron diet, however, developed IDA. We thus conclude that the optimal amount of dietary iron that will not result in iron loading post-weaning in Hamp KOs, while also not causing iron depletion, is ~22 ppm. Consistent with our hypothesis then, Hamp KO rodents require about half as much iron as WT controls.

Support or Funding Information

This investigation was funded by grant DK074867 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (JFC, PI), and grant DK109717 from NIDDK and the Office of Dietary Supplements (to JFC, PI).

lt;pgt;This investigation was funded by grant DK074867 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (JFC, PI), and grant DK109717 from NIDDK and the Office of Dietary Supplements (to JFC, PI).amp;nbsp;lt;/pgt;