Development of a zebrafish model of congenital anemia and drug screening

Diamond–Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by diminished numbers of erythroid pro-genitors. Although it is known that the ribosome is involved in the DBA onset, the molecular pathogenesis of this disease remains unknown and there are no clinically effective treatments available. We developed a zebrafish model of DBA and analyzed the pathogenic mechanism of this disease using this model. Zebrafish has many advantages in studying disease mechanisms, including the fast development and transparency of its embryos and its features conserved in humans. In addition, in vivo chemical screenings enable us to efficiently identify drug candidates. In this review, we introduce our approach to understand the pathogenic mechanism of DBA and to discover drug candidates using zebrafish as an animal model.

[1]  A. Aspesi,et al.  Rare ribosomopathies: insights into mechanisms of cancer , 2019, Nature Reviews Cancer.

[2]  S. Corey,et al.  Peering through zebrafish to understand inherited bone marrow failure syndromes , 2018, Haematologica.

[3]  Beryl B. Cummings,et al.  The Genetic Landscape of Diamond-Blackfan Anemia , 2018, bioRxiv.

[4]  Jesse M. Engreitz,et al.  Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis , 2018, Cell.

[5]  N. Kenmochi,et al.  Exome sequencing identified RPS15A as a novel causative gene for Diamond-Blackfan anemia , 2017, Haematologica.

[6]  N. Kenmochi,et al.  Loss of function mutations in RPL27 and RPS27 identified by whole‐exome sequencing in Diamond‐Blackfan anaemia , 2015, British journal of haematology.

[7]  P. Gleizes,et al.  Diamond Blackfan anemia: ribosomal proteins going rogue. , 2011, Seminars in hematology.

[8]  T. Hara,et al.  Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia , 2010, Haematologica.

[9]  B. Ebert,et al.  Ribosomopathies: human disorders of ribosome dysfunction. , 2010, Blood.

[10]  A. Chakraborty,et al.  Deficiency of ribosomal protein S19 during early embryogenesis leads to reduction of erythrocytes in a zebrafish model of Diamond-Blackfan anemia. , 2008, Human molecular genetics.

[11]  S. Karlsson,et al.  Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference , 2008, British journal of haematology.

[12]  B. Murtaza,et al.  Paroxysmal nocturnal hemoglobinuria. , 2008, Journal of the College of Physicians and Surgeons--Pakistan : JCPSP.

[13]  A. Chakraborty,et al.  Ribosomal Protein Gene Knockdown Causes Developmental Defects in Zebrafish , 2006, PloS one.

[14]  J. Lipton,et al.  Improving clinical care and elucidating the pathophysiology of Diamond Blackfan anemia: An update from the Diamond Blackfan Anemia Registry , 2006, Pediatric blood & cancer.

[15]  S. Karlsson,et al.  Targeted Disruption of the Ribosomal Protein S19 Gene Is Lethal Prior to Implantation , 2004, Molecular and Cellular Biology.

[16]  Peter Gustavsson,et al.  The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia , 1999, Nature Genetics.