A mouse model for an erythropoietin-deficiency anemia

BM Zeigler, J Vajdos, W Qin… - Disease models & …, 2010 - journals.biologists.com
BM Zeigler, J Vajdos, W Qin, L Loverro, K Niss
Disease models & mechanisms, 2010journals.biologists.com
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 …
Summary
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, EpoKO/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 EpoKO/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.
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