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RPL5 Deficiency in Diamond-Blackfan Anemia

DISCOVERIES (ISSN 2359-7232), 2019, July-September issue

CITATION: 

Kazerounian S, Yuan D, Alexander MS, Beggs AH, Gazda HT. Rpl5-Inducible Mouse Model  for Studying Diamond-Blackfan Anemia. Discoveries 2019, 7(3): e96. DOI: 10.15190/d.2019.9

Submitted: July 3rd, 2019; Revised: September 9th, 2019; Accepted: September 10th, 2019; Published: September 30th, 2019; 

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Rpl5-Inducible Mouse Model  for Studying Diamond-Blackfan Anemia

Shideh Kazerounian (1, 3, *), Daniel Yuan (1), Matthew S. Alexander (2), Alan H. Beggs (1, 3, *), Hanna T. Gazda (1, 3)

(1) Boston Children's Hospital, Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston, MA, USA 

(2) University of Alabama at Birmingham and Children’s of Alabama, Departments of Pediatrics and Genetics, Division of Neurology, Birmingham, AL, USA

(3) Harvard Medical School, Boston, MA, USA

*Corresponding author: Shideh Kazerounian, PhD, and Alan H. Beggs, PhD, Boston Children's Hospital, Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston, CLS 15th Floor, 300 Longwood Avenue; Boston, MA 02115; Phone: 617-919-217; Emails: shideh.kazerounian@childrens.harvard.edu and beggs@enders.tch.harvard.edu respectively.

Abstract

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.


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References

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