Mouse genetic background impacts both on iron and non-iron metals parameters and on their relationships

Abstract

Iron is reported to interact with other metals. In addition, it has been shown that genetic background may impact iron metabolism. Our objective was to characterize, in mice of three genetic backgrounds, the links between iron and several non-iron metals. Thirty normal mice (C57BL/6, Balb/c and DBA/2; n = 10 for each group), fed with the same diet, were studied. Quantification of iron, zinc, cobalt, copper, manganese, magnesium and rubidium was performed by ICP/MS in plasma, erythrocytes, liver and spleen. Transferrin saturation was determined. Hepatic hepcidin1 mRNA level was evaluated by quantitative RT-PCR. As previously reported, iron parameters were modulated by genetic background with significantly higher values for plasma iron parameters and liver iron concentration in DBA/2 and Balb/c strains. Hepatic hepcidin1 mRNA level was lower in DBA/2 mice. No iron parameter was correlated with hepcidin1 mRNA levels. Principal component analysis of the data obtained for non-iron metals indicated that metals parameters stratified the mice according to their genetic background. Plasma and tissue metals parameters that are dependent or independent of genetic background were identified. Moreover, relationships were found between plasma and tissue content of iron and some other metals parameters. Our data: (i) confirms the impact of the genetic background on iron parameters, (ii) shows that genetic background may also play a role in the metabolism of non-iron metals, (iii) identifies links between iron and other metals parameters which may have implications in the understanding and, potentially, the modulation of iron metabolism.

Distinct iron homeostasis in C57BL/6 and Balb/c mouse strains

“…Aside from these immunological differences, BL6 and Balb/c mice also segregate from one another in their nutritional biochemistry, especially in regards to their iron management. We noted two previous studies from Cavey et al (Cavey et al., 2015) and Hahn et al (Hahn et al., 2009) that describe an intriguing association between iron homeostasis with the Th1/Th2 and M1/M2 bias of BL6 and Balb/c strains. Though both studies observed that Balb/c mice harbor more plasma and tissue iron than BL6 mice, they did not assess the underlying factors nor the expression of key iron regulatory genes that could explain the iron disparity in these mice.…”

“…Thus, we undertake this study to further explore whether the distinct iron levels in two widely used mouse models in biomedical research could be explained by the differences in the expression of major transporters/enzymes that maintain iron homeostasis. As previously reported (Cavey et al., 2015; Hahn et al., 2009), circulating and tissue iron levels of Balb/c mice were 2‐fold higher compared to BL6 mice; yet, the underlying factors contributing to their disparate iron status are not well‐elucidated. Consistent with their higher iron status, Balb/c mice displayed a higher iron absorption capacity on both apical ( Dcytb and DMT1 ) and basolateral ( Fpn and Heph ) compartments on duodenal epithelial cells.…”

“…The genetic differences between BL6 and Balb/c mice are certainly a confounding factor and this has led many studies to employ only either one of those strains. Nevertheless, many studies have sought to compare and contrast their strain‐level differences as a model to study the effects of genetic heterogeneity on various disorders (Sellers, Clifford, Treuting, & Brayton, 2012) and, more recently, on their nutritional biochemistry such as iron metabolism (Cavey et al., 2015; Hahn et al., 2009). Taken together, this study advances our knowledge on iron homeostasis in BL6 and Balb/c mice, particularly in elucidating how differential expression in key iron regulatory genes could explain their disparate iron status and hypoferremic response to acute inflammation.…”

“…While the immunological disparity between BL6 and Balb/c mice has been widely studied, not much is known on whether these inbred mouse strains can vary with respect to their nutritional biochemistry. Previous studies demonstrate that Balb/c mice exhibit higher levels of serum and tissue iron (Cavey et al., 2015; Hahn et al., 2009). Herein, we document that the distinct iron status between BL6 and Balb/c mice is associated with key differences in iron absorption and regulation at the tissue (i.e., duodenum, liver) and cellular (i.e., neutrophils, macrophages, enterocytes) levels.…”

New growth media for oral bacteria

“…A core composition sufficient for the growth of P. gingivalis (MMBC-1) was further supplemented with components necessary for the growth of T. denticola and S. gordonii (MMBC-3). The quantification of iron in the MMBC media was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), on X-Series II from Thermo Scientific® equipped with collision cell technology (AEM2 Facility, University of Rennes 1), as previously described (Cavey et al, 2015). All three media contained less than 0.56 µM of iron (Table 1), making them suitable for iron metabolism/transport related studies.…”