PUBLICATION

Knockdown of prothrombin in zebrafish

Authors
Day, K., Krishnegowda, N., and Jagadeeswaran, P.
ID
ZDB-PUB-040216-20
Date
2004
Source
Blood cells, molecules & diseases   32(1): 191-198 (Journal)
Registered Authors
Day, Kenneth, Jagadeeswaran, Pudur
Keywords
none
MeSH Terms
  • Animals
  • Congenital Abnormalities/etiology
  • Congenital Abnormalities/genetics
  • Embryo, Nonmammalian
  • Hemorrhage/etiology
  • Hemorrhage/genetics
  • Hemostasis
  • In Situ Hybridization
  • Larva
  • Models, Animal
  • Oligodeoxyribonucleotides, Antisense/genetics*
  • Phenotype
  • Prothrombin/genetics*
  • Prothrombin/physiology*
  • Vertebrates/growth & development
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology
PubMed
14757435 Full text @ Blood Cells Mol. Dis.
Abstract
Thrombin is a serine protease generated from its zymogen, prothrombin, and plays a central role in the coagulation cascade. It is also important for mammalian development. The zebrafish has now been established as an excellent genetic model for studies on mammalian hemostasis and development. In this report, we used prothrombin-specific antisense morpholinos to knock down the levels of prothrombin to characterize the effects of prothrombin deficiency in the zebrafish embryo. Prothrombin morpholino-injected zebrafish embryos yielded an early phenotype exhibiting severe abnormalities that later showed occasional bleeding. In a second late phenotype, the embryos had no observable morphological abnormalities in early stages, but showed occasional bleeding at later stages. These phenotypes resembled characteristics shown by prothrombin knockout mice. Laser-induced vascular injury on some of the normal appearing phenotypic larvae showed a prolonged time to occlusion, and recombinant zebrafish prothrombin injected into these larvae restored a normal time to occlusion thus showing the specificity of the morpholino effect. The system developed here should be useful for investigation of the role of thrombin in vertebrate development.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping