Reduced erythroid cell and erythropoietin production in response to acute anemia in prion protein-deficient (Pmp-/-) mice

Cellular prion protein (PrPc) participates in the pathogenesis of priori diseases but its normal function remains unclear. PrPc is expressed on hematopoietic cells, including erythroid precursors. We investigated the role of PrPc in erythropoiesis in vivo with phenylhydrazine-induced acute anemia. Induction of equivalent anemia in wild-type (WT) and Pmp-/- mice resulted in a higher number of circulating reticulocytes, hematocrits, and spleen weights in WT mice than in Pmp-/- mice on Days 5 and 7. Examination of bone marrow erythroid precursor cells (Terl 19+) on Day 5 revealed no significant differences in the number of these cells between the two types of animals. However, a higher percentage of Terl 19+ cells were going through apoptosis in Pmp-/- mice than in WT mice. Plasma crythropoietin (Epo) levels and Epo mRNA in kidneys peaked on Day 3 in response to anemia for both types of animals but rose less in Pmp-/- (5500 pg/ml) than in WT (18,000 pg/ml) animals. Administration of recombinant human Epo to mice produced an equivalent reticulocyte response in both types of animals suggesting that the potential for erythroid generation is intact in Pmp-/- animals. These observations indicate that PrPc may modulate tissue hypoxia-sensing mechanisms or effect hypoxia target gene expression. Published by Elsevier Inc.