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

Abstract

C57BL/6 (BL6) and Balb/c mice exhibit prototypical Th1‐ and Th2‐dominant immune predispositions, respectively. Iron is a proinflammatory metal ion; however, limited information is documented on the differences in iron homeostasis between BL6 and Balb/c strains. The objective of this study was to investigate the extent to which strain‐level differences in these mice dictates the regulation of iron homeostasis during physiologic and inflammatory conditions. At basal levels, Balb/c mice displayed significantly higher levels of iron in systemic circulation and tissue compared to BL6 mice. Moreover, Balb/c mice had greater iron absorption as indicated by higher gene expressions of duodenal DcytB, DMT1, Fpn, SFT, and Heph. Similarly, hepatic Tf, TfR1, TfR2, and DMT1 expressions were augmented in Balb/c mice. Interestingly, there was no change in hepatic Hamp expression between the two strains, suggesting that the disparity in their maintenance of iron is independent of hepcidin. Additionally, the basal levels of intracellular labile iron pool in Balb/c intestinal epithelial cells, and bone marrow‐derived macrophages and neutrophils, were higher compared to BL6 mice. When mice were challenged with lipopolysaccharide, the acute inflammatory response in BL6 mice was more pronounced than in Balb/c mice, as indicated by the more rapid development of hypoferremia and upregulation of serum IL‐6 and TNF‐α levels in BL6 mice. In conclusion, this study underscores that iron homeostasis is distinct between BL6 and Balb/c strains under both physiologic and inflammatory conditions.

B cell–activating factor modulates the factor VIII immune response in hemophilia A

“…To avoid strain-specific results and limit the potential bias in the assessment of the immune responses, we used distinct HA strains on a C57Bl/6-129 background (colony at CHOP) or BALB/c background (colony at Indiana University). The HA phenotype is similar between these strains but immune responses to pathogens, proteins, and gene therapy is known to differ (58)(59)(60)(61)(62)(63). Further, we used two distinct murine (m) BAFF mAbs: 1) clone 10F4 which is a hamster IgG1 mAb with a half-life of ~2 weeks 64) and 2clone Sandy-2 which is a mouse IgG1 mAb with a half-life of ~10 days (65).…”

Comparison of the effects of high dietary iron levels on bone microarchitecture responses in the mouse strains 129/Sv and C57BL/6J

“…However, this alone was insufficient to induce bone loss under normal conditions in C57BL/6J, implying that the bone could adapt to prevent cell damage caused by iron overload, as the iron content in bone/bone marrow tissues remains unchanged. Moreover, previous reports have indicated that C57BL/6J mice exhibit unique iron characteristics primarily associated with differences in iron absorption capacity on duodenal epithelial cells and iron regulation at the tissue and cellular levels through the expression of hepatic transferrin receptors and ferritin, suggesting that this strain may have a lower capacity for iron uptake and storage in the liver compared to other inbred strains like Balb/c mice 33 . Furthermore, previous reports have indicated that iron accumulation and its effect can vary among different mouse strains, showing that strain differences strongly influence hepatic iron accumulation resulting from an iron-supplemented diet 34 .…”

Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3

“… 30 In this study, mice on a C57BL/6 background were used, whereas Zhang et al characterized the effect of HJV overexpression in mice on a 129/SvEvTac background. Mice with a different genetic background show differences in iron homeostasis 31 , and it is suggested that the contradictory results are a result of the different genetic mouse backgrounds used in both studies.…”