Community Action Needed: Please respond to the NIH RFI
ZFIN ID: ZDB-PUB-080728-15
Deficiency of ribosomal protein S19 during early embryogenesis leads to reduction of erythrocytes in a zebrafish model of Diamond-Blackfan anemia
Uechi, T., Nakajima, Y., Chakraborty, A., Torihara, H., Higa, S., and Kenmochi, N.
Date: 2008
Source: Human molecular genetics   17(20): 3204-3211 (Journal)
Registered Authors: Kenmochi, Naoya, Uechi, Tamayo
Keywords: none
MeSH Terms:
  • Anemia, Diamond-Blackfan/blood*
  • Anemia, Diamond-Blackfan/embryology*
  • Anemia, Diamond-Blackfan/genetics
  • Animals
  • Base Sequence
  • DNA Primers/genetics
  • Disease Models, Animal
  • Erythropoiesis/genetics
  • Gene Targeting
  • Humans
  • Mutation
  • Phenotype
  • RNA, Antisense/genetics
  • RNA, Messenger/biosynthesis
  • RNA, Messenger/genetics
  • Ribosomal Proteins/blood
  • Ribosomal Proteins/deficiency*
  • Ribosomal Proteins/genetics
  • Zebrafish/blood*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/blood
  • Zebrafish Proteins/deficiency*
  • Zebrafish Proteins/genetics*
PubMed: 18653748 Full text @ Hum. Mol. Genet.
Ribosomes are responsible for protein synthesis in all cells. Ribosomal protein S19 (RPS19) is one of the 79 ribosomal proteins in vertebrates. Heterozygous mutations in RPS19 have been identified in 25% of patients with Diamond-Blackfan anemia (DBA), but the relationship between RPS19 mutations and the pure red-cell aplasia of DBA is unclear. In this study, we developed an RPS19-deficient zebrafish by knocking down rps19 using a Morpholino antisense oligo. The RPS19-deficient animals showed a dramatic decrease in blood cells as well as deformities in the head and tail regions at early developmental stages. These phenotypes were rescued by injection of zebrafish rps19 mRNA, but not by injection of rps19 mRNAs with mutations that have been identified in DBA patients. Our results indicate that rps19 is essential for hematopoietic differentiation during early embryogenesis. The effects were specific to rps19, but knocking down the genes for three other ribosomal proteins, rpl35, rpl35a, and rplp2, produced similar phenotypes, suggesting that these genes might have a common function in zebrafish erythropoiesis. The RPS19-deficient zebrafish will provide a valuable tool for investigating the molecular mechanisms of DBA development in humans.