Abstract
Erythropoietin regulates erythropoiesis in a hypoxia-inducible manner. Here we generate inherited super-anaemic mice (ISAM) as a mouse model of adult-onset anaemia caused by erythropoietin deficiency. ISAM express erythropoietin in the liver but lack erythropoietin production in the kidney. Around weaning age, when the major erythropoietin-producing organ switches from the liver to the kidney, ISAM develop anaemia due to erythropoietin deficiency, which is curable by administration of recombinant erythropoietin. In ISAM severe chronic anaemia enhances transgenic green fluorescent protein and Cre expression driven by the complete erythropoietin-gene regulatory regions, which facilitates efficient labelling of renal erythropoietin-producing cells. We show that the majority of cortical and outer medullary fibroblasts have the innate potential to produce erythropoietin, and also reveal a new set of erythropoietin target genes. ISAM are a useful tool for the evaluation of erythropoiesis-stimulating agents and to trace the dynamics of erythropoietin-producing cells.
| Original language | English (US) |
|---|---|
| Article number | 1950 |
| Journal | Nature communications |
| Volume | 4 |
| DOIs | |
| State | Published - Jun 3 2013 |
Funding
Supplementary Information accompanies this paper at http://www.nature.com/ naturecommunications Competing financial interests: This work was supported in part by the research fund from Chugai Pharmaceutical Co. Ltd (Tokyo, Japan). We thank Naoshi Obara (University of Tsukuba), Fumiki Katsuoka, Masanobu Morita and Yuko Kurokouchi (Tohoku University) for their technical supports. We also thank Dr Maggie Patient for editing our manuscript, and Biomedical Research Core and Centre for Laboratory Animal Research of Tohoku University for supports. This work was supported in part by Grants-in-Aids from JSPS (N.S., N.M., M.Y.), JST CREST (M.Y.), JST A-STEP (M.Y.), Tokyo Biochemical Research Foundation (N.S.), The Kidney Foundation Japan (T.S.), Tohoku University Global COE Programme (M.Y.), the NAITO foundation (M.Y.), and the Takeda Science Foundation (M.Y.). We are grateful to Chugai Pharmaceutical Co., Ltd. for comments and suggestions. S.Y. and T.S. are JSPS Research Fellows.
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy