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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, whi...

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Autores principales: Kazerounian, Shideh, Yuan, Daniel, Alexander, Matthew S., Beggs, Alan H., Gazda, Hanna T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Applied Systems srl 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086081/
https://www.ncbi.nlm.nih.gov/pubmed/32309614
http://dx.doi.org/10.15190/d.2019.9
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author Kazerounian, Shideh
Yuan, Daniel
Alexander, Matthew S.
Beggs, Alan H.
Gazda, Hanna T.
author_facet Kazerounian, Shideh
Yuan, Daniel
Alexander, Matthew S.
Beggs, Alan H.
Gazda, Hanna T.
author_sort Kazerounian, Shideh
collection PubMed
description 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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spelling pubmed-70860812020-04-17 Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia Kazerounian, Shideh Yuan, Daniel Alexander, Matthew S. Beggs, Alan H. Gazda, Hanna T. Discoveries (Craiova) Discoveries in Images 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. Applied Systems srl 2019-09-30 /pmc/articles/PMC7086081/ /pubmed/32309614 http://dx.doi.org/10.15190/d.2019.9 Text en Copyright: © 2019, Kazerounian et al. and Applied Systems http://creativecommons.org/licenses/by/4.0/ This article is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Discoveries in Images
Kazerounian, Shideh
Yuan, Daniel
Alexander, Matthew S.
Beggs, Alan H.
Gazda, Hanna T.
Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia
title Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia
title_full Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia
title_fullStr Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia
title_full_unstemmed Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia
title_short Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia
title_sort rpl5-inducible mouse model for studying diamond-blackfan anemia
topic Discoveries in Images
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086081/
https://www.ncbi.nlm.nih.gov/pubmed/32309614
http://dx.doi.org/10.15190/d.2019.9
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