Erythroid-specific expression of the erythropoietin receptor rescued its null mutant mice from lethality

Suzuki, Norio; Onodera, Osamu; Takahashi, Satoru; Higuchi, M.; Mukai, Harumi Y.; Nakahata, Tatsutoshi; Imagawa, Shigehiko; Yamamoto, Masayuki

doi:10.1182/blood-2002-01-0124

Cited by 198 publications

(194 citation statements)

References 29 publications

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“…In contrast, transgenic complementation rescue analyses of EpoR gene revealed that EpoR expression in non-haematopoietic tissues is dispensable for mouse survival and fertility 17 . Thus, while Epo also has nonhaematopoietic functions under pathological or stress conditions, the principal role of Epo is to support erythropoiesis.…”

mentioning

confidence: 88%

Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis

et al. 2013

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Erythropoietin (Epo) supports both primitive erythropoiesis in the yolk sac and definitive erythropoiesis in the fetal liver and bone marrow. Although definitive erythropoiesis requires kidney-and liver-secreted Epo, it is unclear which cells produce Epo for primitive erythropoiesis. Here we find neural Epo-producing (NEP) cells in mid-gestational stage embryos using mouse lines that express green fluorescent protein (GFP) under the Epo gene regulation. In these mice, GFP is expressed exclusively in a subpopulation of neural and neural crest cells at embryonic day 9.0 when Epo-deficient embryos exhibit abnormalities in primitive erythropoiesis. The GFP-positive NEP cells express Epo mRNA and the ex vivo culture of embryonic day 8.5 neural tubes results in the secretion of Epo, which is able to induce the proliferation and differentiation of yolk sac-derived erythroid cells. These results thus suggest that NEP cells secrete Epo and might support the development of primitive erythropoiesis.

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confidence: 88%

Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis

et al. 2013

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“…However this phenotype may be largely rescued by restoration of EpoR production in hematopoietic tissue (139). Attempts to localize the EpoR within the heart have been made by dissecting of chick embryonic heart into epicardium, myocardium, and endocardium (140).…”

Section: Epo In Treatment Of Brain Diseasesmentioning

confidence: 99%

Epo and Non-hematopoietic Cells: What Do We Know?

Ogunshola

Bogdanova

2013

Methods in Molecular Biology

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“…In addition, there are other results inconsistent with the hypothesis. Mice that were engineered to express EPOR exclusively in hematopoietic cells showed normal size and development, with no effect on development of the vascular endothelium [29]. In experiments designed to detect EPOR-induced signaling in tumor cell lines, including those reported to respond to ESAs by others, no effect was detected [30].…”

Section: Nonhematopoietic Effects Of Erythropoietinmentioning

confidence: 99%

Discovery and basic pharmacology of erythropoiesis-stimulating agents (ESAs), including the hyperglycosylated ESA, darbepoetin alfa: an update of the rationale and clinical impact

Kiss¹,

Elliott

Jedynasty³

et al. 2010

Eur J Clin Pharmacol

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Cloning of the human erythropoietin (EPO) gene and development of the first recombinant human erythropoietin (rHuEPO) drug were truly breakthroughs. This allowed a deeper understanding of the structure and pharmacology of rHuEpo, which in turn inspired the discovery and development of additional erythropoiesisstimulating agents (ESAs). In vivo specific activity and serum half-life of rHuEPO are influenced by the amount and structure of the attached carbohydrate. Increased numbers of sialic acids on carbohydrate attached to rHuEPO correlated with a relative increase in in-vivospecific activity and increased serum half-life. The effect of increasing the number of sialic-acid-containing carbohydrates on in-vivo-specific activity was explored. Initial research focused on solving the problem of how the protein backbone could be engineered so a cell would add more carbohydrate to it. Additional work resulted in darbepoetin alfa, a longer-acting molecule with two additional carbohydrate chains.

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Erythroid-specific expression of the erythropoietin receptor rescued its null mutant mice from lethality

Cited by 198 publications

References 29 publications

Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis

Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis

Epo and Non-hematopoietic Cells: What Do We Know?

Discovery and basic pharmacology of erythropoiesis-stimulating agents (ESAs), including the hyperglycosylated ESA, darbepoetin alfa: an update of the rationale and clinical impact

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