Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 2, 2000
Publication Date: June 1, 2001
Citation: Roughead, Z.K., Finley, J.W. 2001. Mucosal uptake and whole body retention of dietary manganese are not altered in beta2-microglobulin knockout mice. Biological Trace Element Research. 80(3):231-244. Interpretive Summary: Manganese is an essential nutrient, however, currently there is no Recommended Dietary Allowance for this nutrient. The absorption of manganese is thought to be closely related to iron. In this study, we used genetically manipulated mice, which have been used as model for the study of human hemochromatosis. Hemochromatosis is a common genetic disorder that is characterized by iron overload, especially in the liver. We used the defect in these mice to learn more about manganese through its relationship with iron. We found that these mice had a lot more iron in their liver and they continued to accumulate iron as they got older. Despite these marked differences in iron metabolism, we detected no differences in intestinal absorption of manganese or in the amount of manganese in the brain or liver of the mutant mice compared to the normal mice; this indicates that the metabolism of iron and manganese is not completely interdependent. In conclusion, the beta-2 microglobulin knockout mice, which metabolize iron very similar to human hemochromatosis patients, developed iron overload, however, the genetic defect in these mice did not lead to any detectable changes in the metabolism of manganese.
Technical Abstract: To further examine the interrelationships between manganese and iron absorption, the mucosal uptake, initial rate of loss, whole body retention, and tissue distribution of an orally administered 54**Mn radiotracer were compared between normal and beta2-microglobulin knockout (beta2m -/-) mice. Initial uptake of 54**Mn by the intestinal mucosa, the liver, and the brain was not different between the two strains. The mutant mice had much higher concentrations of nonheme and total iron in the liver, but hepatic manganese, copper, magnesium, and zinc concentrations were similar between the two strains. In summary, the mucosal uptake and whole body retention of manganese, and tissue manganese concentrations were not altered in beta2m (-/-) mice; this suggests that normal homeostasis of manganese is not affected by the altered HFE protein- beta2m complex in these mice.