A mouse model of adult-onset anaemia dueto erythropoietin deficiency

摘要

Erythropoietin regulates erythropoiesis in a hypoxia-inducible manner. Here we generateinherited super-anaemic mice (ISAM) as a mouse model of adult-onset anaemia caused byerythropoietin deficiency. ISAM express erythropoietin in the liver but lack erythropoietinproduction in the kidney. Around weaning age, when the major erythropoietin-producingorgan switches from the liver to the kidney, ISAM develop anaemia due to erythropoietindeficiency, which is curable by administration of recombinant erythropoietin. In ISAM severechronic anaemia enhances transgenic green fluorescent protein and Cre expression driven bythe complete erythropoietin-gene regulatory regions, which facilitates efficient labelling ofrenal erythropoietin-producing cells. We show that the majority of cortical and outermedullary fibroblasts have the innate potential to produce erythropoietin, and also reveal anew 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.