Role of Iron Metabolism-Related Genes in Prenatal Development: Insights from Mouse Transgenic Models
Abstract
:1. Introduction
2. Iron Handling in a Mouse Embryo during Preimplantation Development
3. Iron Metabolism Proteins in Mouse Post-Implantation Development
4. Heme-Related Genes in Mouse Prenatal Development
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Gene Product | Function | Phenotype | Reference |
---|---|---|---|---|
Fth1 | Ferritin (Ft) H-subunit | Ferroxidase activity, essential for iron uptake by the ferritin molecule | Lethality from E3.5 to E9.5 | [13] |
Ftl1 | Ferritin (Ft) L-subunit | Has a nucleation site involved in iron-core formation inside the protein envelope | Partial (about 50%) lethality at E11.5–E13.5 | [14] |
Tfr1 | Transferrin receptor 1 | Import of iron from transferrin into cells by endocytosis | Lethality after implantation, by E12.5 Affected both erythropoiesis and neurologic development | [15] |
Slc11a2 | Divalent metal ion transporter 1 (DMT1) | Transport of ferrous iron (Fe2+) and some divalent metal ions across the plasma membrane and/or out of the endosomal compartment. | No data about prenatal development. Newborn mice are anemic, without developmental abnormalities. | [16] |
Slc40a1 | Ferroportin (Fpn) | Transport of iron from the inside of a cell to the extracellular environment. | Lethality around E7.5 in embryos with global KO. Rescue of embryonic lethality through selective KO of ferroportin in the embryo proper | [17] |
Aco 1 (Irp1) Irp2 | Iron Regulatory Proteins 1 and 2 | Role in post-transcriptional regulation of several mRNAs encoding iron metabolism proteins | No overt abnormalities in either Irp1 nor Irp2 knockout embryos/fetuses Lethlity of double Irp1 and Irp2 KO embryos at E6.5 and beyond. Functional iron deficiency | [18] |
Hamp1 | Hepcidin | Central regulator of systemic iron homeostasis. Role in the regulation of the entry of iron into the circulation | Global hepcidin knock-out has no effect on placental or fetal liver iron status in iron-replete or iron-deficient pregnancies. Reduction of hepatic iron content, decrease in hemoglobin concentration in liver-specific hepcidin KO embryos Severe microcytic anemia in fetuses with transgenic ubiquitous overexpression of the Hamp gene | [19,20,21] 1 |
Tmprss6 | Matriptase-2 | Suppressor of hepatic hepcidin expression | Strongly up-regulated liver hepcidin and decreased placental ferroportin expression. Reduction in total non-heme body iron, and some red blood cell indices in E17.5 fetuses, halmarking iron deficiency and microcytic anemia | [22] |
Hmox1 | Heme oxygenase 1 (HO1) | Role in in the enzymatic breakdown of heme molecules | Abnormal placentation, inadequate remodeling of spiral arteries, intrauterine growth restriction, and eventually fetal lethality | [23] |
Flvcr1 | Feline leukemia virus subgroup C receptor-related protein 1 | Export of cytoplasmic heme to the outside of the cell | Deficient red cell production. Lethality at one of two embryonic times: at or before E7.5 and between E14.5 and E16.5. | [24] |
ISCA1 | Iron-sulfur cluster assembly 1 | Iron-sulfur cluster (Fe-S) carrier, accepting (Fe-S) from a scaffold protein and transferring it to target proteins | Lethality at E8.5 and beyond Damage to the electron transport chain and TCA cycle. | [25] 2 |
Fxn, Frda | Frataxin | Precise function remains unclear. Involvement in Fe-S cluster and heme synthesis, energy conversion and oxidative phosphorylation, iron handling and response to oxidative damage | At E7.5 and E8.5 embryos start to be resorbed and reduced to a small mass of embryonic tissue surrounded by maternal hemmorrhagic tissue Complete resorption at E9.5. | [26] |
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Kopeć, Z.; Starzyński, R.R.; Jończy, A.; Mazgaj, R.; Lipiński, P. Role of Iron Metabolism-Related Genes in Prenatal Development: Insights from Mouse Transgenic Models. Genes 2021, 12, 1382. https://doi.org/10.3390/genes12091382
Kopeć Z, Starzyński RR, Jończy A, Mazgaj R, Lipiński P. Role of Iron Metabolism-Related Genes in Prenatal Development: Insights from Mouse Transgenic Models. Genes. 2021; 12(9):1382. https://doi.org/10.3390/genes12091382
Chicago/Turabian StyleKopeć, Zuzanna, Rafał R. Starzyński, Aneta Jończy, Rafał Mazgaj, and Paweł Lipiński. 2021. "Role of Iron Metabolism-Related Genes in Prenatal Development: Insights from Mouse Transgenic Models" Genes 12, no. 9: 1382. https://doi.org/10.3390/genes12091382
APA StyleKopeć, Z., Starzyński, R. R., Jończy, A., Mazgaj, R., & Lipiński, P. (2021). Role of Iron Metabolism-Related Genes in Prenatal Development: Insights from Mouse Transgenic Models. Genes, 12(9), 1382. https://doi.org/10.3390/genes12091382