title: A mouse model of adult-onset anaemia due to erythropoietin deficiency.
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.
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Souma
authors.forename: Ikuo
authors.initials: I
authors.lastname: Hirano
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Pan
authors.forename: Naoko
authors.initials: N
authors.lastname: Minegishi
authors.forename: Norio
authors.initials: N
authors.lastname: Suzuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D017668:Age of Onset; D000375:Aging / Q000235:genetics / Q000473:pathology*; D000483:Alleles; D000740:Anemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D020964:Embryo Loss / Q000378:metabolism / Q000473:pathology; D004900:Erythroblasts / Q000378:metabolism / Q000473:pathology; D004921:Erythropoietin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D019426:Integrases / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling; D019076:Transgenes / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D004921:Erythropoietin; D049452:Green Fluorescent Proteins; C045073:Cre recombinase; D019426:Integrases