Peering through zebrafish to understand inherited bone marrow failure syndromes

Oyarbide, U., Topczewski, J., Corey, S.J.
Haematologica   104(1): 13-24 (Review)
Registered Authors
Topczewski, Jacek
Bone Marrow Failure, Bone Marrow Microenvironment, Hematopoiesis, organismal models, zebrafish
MeSH Terms
  • Animals
  • Bone Marrow Failure Disorders*/genetics
  • Bone Marrow Failure Disorders*/metabolism
  • Bone Marrow Failure Disorders*/pathology
  • Disease Models, Animal
  • Genetic Diseases, Inborn*/genetics
  • Genetic Diseases, Inborn*/metabolism
  • Genetic Diseases, Inborn*/pathology
  • Humans
  • Tumor Suppressor Protein p53*/genetics
  • Tumor Suppressor Protein p53*/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
30573510 Full text @ Haematologica
Inherited bone marrow failure syndromes are experiments of nature characterized by impaired hematopoiesis with cancer and leukemia predisposition. The mutations associated with inherited bone marrow failure syndromes affect fundamental cellular pathways, such as DNA repair, telomere maintenance, or proteostasis. How these disturbed pathways fail to produce sufficient blood cells and lead to leukemogenesis are not understood. The rarity of inherited cytopenias, paucity of affected primary human hematopoietic cells, and sometime inadequacy of murine or induced pluripotential stem cell models constitute obstacles to greater knowledge of them. Zebrafish proffer an organismal model to study gene functions. As vertebrates, zebrafish share with humans many orthologous genes involved in blood disorders. As a model organism, zebrafish provides advantages, including rapid development of transparent embryos, high fecundity providing large numbers of mutant and normal siblings, and a large collection of mutant and transgenic lines useful in interrogating the blood system and other tissues during development. Importantly, recent advances in genomic editing in zebrafish can speedily validate the new genes or novel variants discovered in clinical investigation as causes for marrow failure. Here we review zebrafish as a model organism that phenocopies Fanconi anemia, Diamond-Blackfan anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, congenital amegakaryocytic thrombocytopenia, and severe congenital neutropenia. Two important insights, provided by modeling inherited cytopenias in zebrafish, is an appreciation for ribosome biogenesis and TP53 in mediating marrow failure and non-hematologic defects. They also suggest that TP53-independent pathways contribute to marrow failure. Zebrafish also provide an attractive organismal system for drug development.
Genes / Markers
Show all Figures
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes