ArticleMolecular and cellular biology2017
Renal Anemia Model Mouse Established by Transgenic Rescue with an Erythropoietin Gene Lacking Kidney-Specific Regulatory Elements.
Article in Molecular and cellular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Crosstalk between oxygen signaling and iron metabolism in renal interstitial fibroblasts.Journal of clinical biochemistry and nutrition · 2024Article
- Expression and Variations inAnimals : an open access journal from MDPI · 2024Article
- Drugs activating hypoxia-inducible factors correct erythropoiesis and hepcidin levels via renal EPO induction in mice.Blood advances · 2023Article
- The transcriptional and regulatory identity of erythropoietin producing cells.Nature medicine · 2023Article
- Article
- Fount, fate, features, and function of renal erythropoietin-producing cells.Pflugers Archiv : European journal of physiology · 2022Review
- Are Alterations in DNA Methylation Related to CKD Development?International journal of molecular sciences · 2022Review
- Fate-mapping of erythropoietin-producing cells in mouse models of hypoxaemia and renal tissue remodelling reveals repeated recruitment and persistent functionality.Acta physiologica (Oxford, England) · 2022Article
- Efficient isolation of interstitial fibroblasts directly from mouse kidneys or indirectly afterSTAR protocols · 2021Article
- Blockade of the interaction between BMP9 and endoglin on erythroid progenitors promotes erythropoiesis in mice.Genes to cells : devoted to molecular & cellular mechanisms · 2021Article
- Erythropoietin in bone homeostasis-Implications for efficacious anemia therapy.Stem cells translational medicine · 2021Article
- Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells.Scientific reports · 2021Article
- Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis.International journal of molecular sciences · 2020Review
- A long hypoxia-inducible factor 3 isoform 2 is a transcription activator that regulates erythropoietin.Cellular and molecular life sciences : CMLS · 2020Article
- Extrahepatic deficiency of transferrin receptor 2 is associated with increased erythropoiesis independent of iron overload.The Journal of biological chemistry · 2020Article
- Update on mutations in the HIF: EPO pathway and their role in erythrocytosis.Blood reviews · 2019Review
- An immortalized cell line derived from renal erythropoietin-producing (REP) cells demonstrates their potential to transform into myofibroblasts.Scientific reports · 2019Article
- Alteration of the DNA Methylation Signature of Renal Erythropoietin-Producing Cells Governs the Sensitivity to Drugs Targeting the Hypoxia-Response Pathway in Kidney Disease Progression.Frontiers in genetics · 2019Review
- The Neural Crest as the First Production Site of the Erythroid Growth Factor Erythropoietin.Frontiers in cell and developmental biology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The erythropoietin (Epo) gene is under tissue-specific inducible regulation. Because the kidney is the primary EPO-producing tissue in adults, impaired EPO production in chronic kidney disorders results in serious renal anemia. The Epo gene contains a liver-specific enhancer in the 3' region, but the kidney-specific enhancer for gene expression in renal EPO-producing (REP) cells remains elusive. Here, we examined a conserved upstream element for renal Epo regulation (CURE) region that spans 17.4 kb to 3.6 kb upstream of the Epo gene and harbors several phylogenetically conserved elements. We prepared various Epo gene-reporter constructs utilizing a bacterial artificial chromosome and generated a number of transgenic-mouse lines. We observed that deletion of the CURE region (δCURE) abrogated Epo gene expression in REP cells. Although transgenic expression of the δCURE construct rescued Epo-deficient mice from embryonic lethality, the rescued mice had severe EPO-dependent anemia. These mouse lines serve as an elaborate model for the search for erythroid stimulatory activity and are referred to as AnRED (anemic model with renal EPO deficiency) mice. We also dissected the CURE region by exploiting a minigene harboring four phylogenetically conserved elements in reporter transgenic-mouse analyses. Our analyses revealed that Epo gene regulation in REP cells is a complex process that utilizes multiple regulatory influences.
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