Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia.

Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow disorder with mutations in ribosomal protein genes. Several animal models have been developed to study the pathological mechanism of DBA. Previously, we reported that the complete knock-out of both Rpl5 and Rps24 alleles were lethal, while heterozygous Rpl5+/- and Rps24+/- mice showed normal phenotype.  To establish a more efficient mouse model for mimicking DBA symptoms, we have taken advantage of RNAi technology to generate an inducible mouse model utilizing tetracycline-induced down-regulation of Rpl5.    After two weeks of treatment with doxycycline in drinking water, a subset of treated shRNA Rpl5+/- adult mice developed mild anemia while control mice had normal complete blood counts. Similarly, treated shRNA Rpl5+/- mice developed reticulocytopenia and bone marrow erythroblastopenia. Detection of DBA symptoms in these mice make them a valuable DBA model for studying the pathological mechanism underlying DBA and for further assessment of the disease and drug testing for novel therapies.