A mouse model for an erythropoietin-deficiency anemia.
In mammals, the production of red blood cells is tightly regulated by the growth factor erythropoietin (EPO). Mice lacking a functional Epo gene are embryonic lethal, and studying erythropoiesis in EPO-deficient adult animals has therefore been limited. In order to obtain a preclinical model for an EPO-deficient anemia, we developed a mouse in which Epo can be silenced by Cre recombinase. After induction of Cre activity, Epo(KO/flox) mice experience a significant reduction of serum EPO levels and consequently develop a chronic, normocytic and normochromic anemia. Furthermore, compared with wild-type mice, Epo expression in Epo(KO/flox) mice is dramatically reduced in the kidney, and expression of a well-known target gene of EPO signaling, Bcl2l1, is reduced in the bone marrow. These observations are similar to the clinical display of anemia in patients with chronic kidney disease. In addition, during stress-induced erythropoiesis these mice display the same recovery rate as their heterozygous counterparts. Taken together, these results demonstrate that this model can serve as a valuable preclinical model for the anemia of EPO deficiency, as well as a tool for the study of stress-induced erythropoiesis during limiting conditions of EPO.
Department of Inflammation, Pfizer Global Research and Development, 700 West Chesterfield Parkway, St Louis, MO 63017, USA.
Brandon M
BM
Zeigler
Janis
J
Vajdos
Wenning
W
Qin
Linda
L
Loverro
Knut
K
Niss
D000740:Anemia / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D004195:Disease Models, Animal; D041905:Erythroid Cells / Q000187:drug effects / Q000473:pathology; D004921:Erythropoietin / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D005434:Flow Cytometry; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D006400:Hematocrit; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins
D012333:RNA, Messenger; D011994:Recombinant Proteins; D004921:Erythropoietin