Article

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 pp.259-264

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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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

clinical expression
 
complete loss
 
congenital disease
 
detailed analysis
 
Diamond-Blackfan anemia
 
different genetic background
 
disrupted Rps19 allele
 
erythrocyte deaminase
 
erythropoietin
 
globin isoforms
 
human ribosomal protein S19 gene
 
major abnormalities
 
markers
 
patients
 
Rps19 levels
 
subclinical phenotypes
 
transcriptional level