Plasma levels of bradykinin are suppressed in factor XII-deficient mice.
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.
Iwaki
Takayuki
T
W. M. Keck Center for Transgene Research, 230 Raclin-Carmichael Hall, University of Notre Dame, IN 46556, USA.
Castellino
Francis J
FJ
D000818:Animals; D001777:Blood Coagulation; D001920:Bradykinin / Q000032:analysis / Q000097:blood*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005172:Factor XI / Q000235:genetics / Q000378:metabolism; D005174:Factor XII / Q000235:genetics* / Q000378:metabolism; D005175:Factor XII Deficiency / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D005374:Filtration; D005786:Gene Expression Regulation; D019679:Kininogen, High-Molecular-Weight / Q000235:genetics / Q000378:metabolism; D008567:Membranes, Artificial; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010314:Partial Thromboplastin Time; D011288:Prekallikrein / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D014018:Tissue Distribution
D019679:Kininogen, High-Molecular-Weight; D008567:Membranes, Artificial; D012333:RNA, Messenger; D005174:Factor XII; D005172:Factor XI; D011288:Prekallikrein; D001920:Bradykinin