Plasma levels of bradykinin are suppressed in factor XII-deficient mice

Thromb Haemost. 2006 Jun;95(6):1003-10. doi: 10.1160/TH06-03-0128.


A genetically-transmissible factor (F) XII-inactivated allele has been produced in mice by targeted replacement of exons 3-8 of the FXII gene with the neomycin resistance gene. Interbreeding of these mice provided offspring homozygous for two inactivated FXII alleles (FXII(-/-)). Male and female FXII-deficient mice bred normally in all genotypic combinations of the heterozygous and homozygous states, and the offspring survived to adulthood, suggesting that a total FXII deficiency does not affect embryonic development and survival. Neither FXII transcripts nor FXII antigen was found in various tissues of adult FXII(-/-) mice. No obvious unchallenged coagulopathies were present in FXII(-/-) adult mice, despite greatly prolonged activated partial thromboplastin times in this mouse cohort. FXII(-/-) mice were then used to assess the in vivo importance of the plasma FXII/prekallikrein/kininogen pathway in provision of resting plasma bradykinin (BK) levels and in generation of plasma BK stimulated by contact with an artificial surface, using a new and greatly improved plasma BK assay developed during these studies. It was found that approximately 50% of resting BK, and all of the contact-stimulated plasma BK, was provided by this FXII-dependent pathway, without a requirement for FXI. These results provide clear evidence that surface-stimulated BK production, in mice, is dependent on the activation of FXII.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Coagulation
  • Bradykinin / analysis
  • Bradykinin / blood*
  • Disease Models, Animal*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Factor XI / genetics
  • Factor XI / metabolism
  • Factor XII / genetics*
  • Factor XII / metabolism
  • Factor XII Deficiency / blood*
  • Factor XII Deficiency / genetics
  • Factor XII Deficiency / metabolism
  • Filtration
  • Gene Expression Regulation
  • Kininogen, High-Molecular-Weight / genetics
  • Kininogen, High-Molecular-Weight / metabolism
  • Membranes, Artificial
  • Mice
  • Mice, Inbred C57BL*
  • Mice, Knockout
  • Partial Thromboplastin Time
  • Prekallikrein / genetics
  • Prekallikrein / metabolism
  • RNA, Messenger / metabolism
  • Radioimmunoassay / methods
  • Tissue Distribution


  • Kininogen, High-Molecular-Weight
  • Membranes, Artificial
  • RNA, Messenger
  • Factor XII
  • Factor XI
  • Prekallikrein
  • Bradykinin