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Erythropoiesis in the Rps19 disrupted mouse: Analysis of erythropoietin response and biochemical markers for Diamond-Blackfan anemia

Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden; Molecular Medicine and Gene Therapy, The Strategic Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden; Unit of Clinical Chemistry, Karolinska Hospital, Huddinge, Sweden; Department of Medical Sciences, Clinical Chemistry, Uppsala Akademiska Hospital, Uppsala, Sweden
Blood Cells, Molecules, and Diseases DOI: 10.1016/j.bcmd.2005.12.002

ABSTRACT The human ribosomal protein S19 gene (RPS19) is mutated in approximately 20% of patients with Diamond-Blackfan anemia (DBA), a congenital disease with a specific defect in erythropoiesis. The clinical expression of DBA is highly variable, and subclinical phenotypes may be revealed by elevated erythrocyte deaminase (eADA) activity only. In mice, complete loss of Rps19 results in early embryonic lethality whereas Rps19+/− mice are viable and without major abnormalities including the hematopoietic system. We have performed a detailed analysis of the Rps19+/− mice. We estimated the Rps19 levels in hematopoietic tissues and we analyzed erythrocyte deaminase activity and globin isoforms which are used as markers for DBA. The effect of a disrupted Rps19 allele on a different genetic background was investigated as well as the response to erythropoietin (EPO). From our results, we argue that the loss of one Rps19 allele in mice is fully compensated for at the transcriptional level with preservation of erythropoiesis.

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