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

• Published in: Thrombosis and haemostasis Vol. 95; no. 6; p. 1003
• Main Authors: Iwaki, Takayuki, Castellino, Francis J
• Format: Journal Article
• Language: English
• Published: Germany 01.06.2006
• Subjects: 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; Radioimmunoassay - methods; RNA, Messenger - metabolism; Tissue Distribution
• ISSN: 0340-6245
• 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.