PUBLICATION

Loss of fibrinogen in zebrafish results in symptoms consistent with human hypofibrinogenemia

Authors
Vo, A.H., Swaroop, A., Liu, Y., Norris, Z.G., and Shavit, J.A.
ID
ZDB-PUB-131018-2
Date
2013
Source
PLoS One   8(9): e74682 (Journal)
Registered Authors
Liu, Yang, Shavit, Jordan, Vo, Andy
Keywords
none
MeSH Terms
  • Zebrafish*
  • In Situ Hybridization
  • Afibrinogenemia/physiopathology*
  • Morpholinos/metabolism
  • DNA Primers
  • Blood Coagulation/genetics*
  • Blood Coagulation/physiology
  • Hemorrhage/pathology
  • Gene Knockdown Techniques
  • Fibrinogen/genetics
  • Fibrinogen/metabolism*
  • Humans
  • Animals
  • Disease Models, Animal*
  • Phenotype*
(all 15)
PubMed
24098662 Full text @ PLoS One
Abstract

Cessation of bleeding after trauma is a necessary evolutionary vertebrate adaption for survival. One of the major pathways regulating response to hemorrhage is the coagulation cascade, which ends with the cleavage of fibrinogen to form a stable clot. Patients with low or absent fibrinogen are at risk for bleeding. While much detailed information is known about fibrinogen regulation and function through studies of humans and mammalian models, bleeding risk in patients cannot always be accurately predicted purely based on fibrinogen levels, suggesting an influence of modifying factors and a need for additional genetic models. The zebrafish has orthologs to the three components of fibrinogen (fga, fgb, and fgg), but it hasn’t yet been shown that zebrafish fibrinogen functions to prevent bleeding in vivo. Here we show that zebrafish fibrinogen is incorporated into an induced thrombus, and deficiency results in hemorrhage. An Fgb-eGFP fusion protein is incorporated into a developing thrombus induced by laser injury, but causes bleeding in adult transgenic fish. Antisense morpholino knockdown results in intracranial and intramuscular hemorrhage at 3 days post fertilization. The observed phenotypes are consistent with symptoms exhibited by patients with hypo- and afibrinogenemia. These data demonstrate that zebrafish possess highly conserved orthologs of the fibrinogen chains, which function similarly to mammals through the formation of a fibrin clot.

Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mi4001TgTransgenic Insertion
    sd2TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      fgaMO1-fgaMRPHLNO
      fgbMO1-fgbMRPHLNO
      fggMO1-fggMRPHLNO
      1 - 3 of 3
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      Fish
      Antibodies
      Orthology
      Engineered Foreign Genes
      Marker Marker Type Name
      DsRedEFGDsRed
      EGFPEFGEGFP
      1 - 2 of 2
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      Mapping