ArticlePloS one2012
ZIP8 zinc transporter: indispensable role for both multiple-organ organogenesis and hematopoiesis in utero.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 99 citations in OpenAlex.
- Synergistic interaction between lead and cadmium via metal-transporter gene upregulation in mice.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Manganese: biology, physiology and role in disease.Cell discovery · 2026Review
- Nutrigenomic profiling identifies ZIP10 (Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Metabolic alterations and redox homeostasis in ferroptosis: emerging mechanisms and therapeutic implications.Archives of medical science : AMS · 2026Article
- Removal of Toxic Metabolites-Chelation: Manganese Disorders.Journal of inherited metabolic disease · 2025Review
- A genome-wide association study identifies novel genetic variants associated with neck or shoulder pain in the UK biobank (N = 430,193).Pain reports · 2025Article
- Intestinal E. coli-produced yersiniabactin promotes profibrotic macrophages in Crohn's disease.Cell host & microbe · 2025Article
- Intestinal ZIP8 Regulates Tissue Manganese Distribution and Modifies Manganese Overload in ZIP14 Deficiency.Journal of nutrition and metabolism · 2025Article
- Article
- Iron Supplementation of Pregnant Sows to Prevent Iron Deficiency Anemia in Piglets: A Procedure of Questionable Effectiveness.International journal of molecular sciences · 2024Review
- Iron Homeostasis During Pregnancy: Maternal, Placental, and Fetal Regulatory Mechanisms.Annual review of nutrition · 2023Review
- Membrane Transporters Involved in Iron Trafficking: Physiological and Pathological Aspects.Biomolecules · 2023Review
- The Regulation of ZIP8 by Dietary Manganese in Mice.International journal of molecular sciences · 2023Article
- Iron homeostasis and post-hemorrhagic hydrocephalus: a review.Frontiers in neurology · 2023Review
- The schizophrenia-associated missense variant rs13107325 regulates dendritic spine density.Translational psychiatry · 2022Article
- Iron Metabolism and Ferroptosis in Physiological and Pathological Pregnancy.International journal of molecular sciences · 2022Review
- Clinical and Molecular Aspects of Iron Metabolism in Failing Myocytes.Life (Basel, Switzerland) · 2022Review
- Ferroptosis in viral infection: the unexplored possibility.Acta pharmacologica Sinica · 2022Review
- Review
- Zinc transporters ZIPT-2.4 and ZIPT-15 are required for normal C. elegans fecundity.Journal of assisted reproduction and genetics · 2022Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Previously this laboratory characterized Slc39a8-encoded ZIP8 as a Zn(2+)/(HCO(3)(-))(2) symporter; yet, the overall physiological importance of ZIP8 at the whole-organism level remains unclear. Herein we describe the phenotype of the hypomorphic Slc39a8(neo/neo) mouse which has retained the neomycin-resistance gene in intron 3, hence causing significantly decreased ZIP8 mRNA and protein levels in embryo, fetus, placenta, yolk sac, and several tissues of neonates. The Slc39a8(neo) allele is associated with diminished zinc and iron uptake in mouse fetal fibroblast and liver-derived cultures; consequently, Slc39a8(neo/neo) newborns exhibit diminished zinc and iron levels in several tissues. Slc39a8(neo/neo) homozygotes from gestational day(GD)-11.5 onward are pale, growth-stunted, and die between GD18.5 and 48 h postnatally. Defects include: severely hypoplastic spleen; hypoplasia of liver, kidney, lung, and lower limbs. Histologically, Slc39a8(neo/neo) neonates show decreased numbers of hematopoietic islands in yolk sac and liver. Low hemoglobin, hematocrit, red cell count, serum iron, and total iron-binding capacity confirmed severe anemia. Flow cytometry of fetal liver cells revealed the erythroid series strikingly affected in the hypomorph. Zinc-dependent 5-aminolevulinic acid dehydratase, required for heme synthesis, was not different between Slc39a8(+/+) and Slc39a8(neo/neo) offspring. To demonstrate further that the mouse phenotype is due to ZIP8 deficiency, we bred Slc39a8(+/neo) with BAC-transgenic BTZIP8-3 line (carrying three extra copies of the Slc39a8 allele); this cross generated viable Slc39a8(neo/neo)_BTZIP8-3(+/+) pups showing none of the above-mentioned congenital defects-proving Slc39a8(neo/neo) causes the described phenotype. Our study demonstrates that ZIP8-mediated zinc transport plays an unappreciated critical role during in utero and neonatal growth, organ morphogenesis, and hematopoiesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.