Enhanced blood coagulation and fibrinolysis in mice lacking histidine-rich glycoprotein (HRG)

J Thromb Haemost. 2005 May;3(5):865-72. doi: 10.1111/j.1538-7836.2005.01238.x.


Histidine-rich glycoprotein (HRG) is a serum protein belonging to the cystatin superfamily. HRG may play a regulatory role in hemostasis and innate immunity. However, this role is uncertain because of a lack of rigorous testing in an animal model. We generated mice lacking the translation start point of exon 1 of the Hrg gene, effectively resulting in a null mutation (Hrg-/-). The mice were viable and fertile but had no HRG in their blood. Antithrombin activity in the plasma of Hrg-/- mice was higher than in the plasma of heterozygous Hrg+/- or wild-type Hrg+/+ mice. The prothrombin time was shorter in Hrg-/- mice than in Hrg+/- and Hrg+/+ mice. Bleeding time after tail tip amputation in Hrg-/- mice was shorter than in Hrg+/+ mice. The spontaneous fibrinolytic activity in clotted blood of Hrg-/- mice was higher than in Hrg+/+ mice. These findings suggest that HRG plays a role as both an anticoagulant and an antifibrinolytic modifier, and may regulate platelet function in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleeding Time
  • Blood Coagulation*
  • Blood Platelets / physiology
  • Blotting, Southern
  • Cloning, Molecular
  • Exons
  • Fibrinolysis
  • Genetic Vectors
  • Genotype
  • Heterozygote
  • Mice
  • Mice, Transgenic
  • Models, Genetic
  • Molecular Sequence Data
  • Protein Binding
  • Proteins / genetics*
  • Proteins / physiology*
  • Skin / metabolism
  • Stem Cells
  • Wound Healing


  • Proteins
  • histidine-rich proteins

Associated data

  • GENBANK/AB055898