Characterization of mouse thrombin-activatable fibrinolysis inhibitor.
Based on in vitro studies, thrombin-activatable fibrinolysis inhibitor (TAFI) has been hypothesized as a link between coagulation and fibrinolysis, but the physiological role of TAFI in vivo has not yet been established. To anticipate on the availability of genetically modified mouse models, we studied the endogenous expression of TAFI in mice. Functional TAFI was found in mouse plasma. TAFI mRNA was only detectable in the liver, showing a hepatocyte-specific expression with a pericentral lobular distribution pattern. The murine TAFI cDNA was cloned and sequenced. The deduced amino acid sequence revealed that murine TAFI is highly identical to human TAFI. The murine cDNA was stably expressed and the activated recombinant protein was functionally active; it converted the substrate hippuryl-arginine, and prolonged the clot lysis time of TAFI depleted plasma. We conclude that mice have functional TAFI in plasma, which is highly similar to human TAFI. Therefore, genetically modified mice may provide useful models to study the role of TAFI in vivo.
Marx
P F
PF
Department of Haematology, University Medical Center, Utrecht, The Netherlands. P.F.Marx@lab.azu.nl
Wagenaar
G T
GT
Reijerkerk
A
A
Tiekstra
M J
MJ
van Rossum
A G
AG
Gebbink
M F
MF
Meijers
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D000933:Antifibrinolytic Agents / Q000097:blood; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D001777:Blood Coagulation / Q000187:drug effects; D015153:Blotting, Western; D025901:Carboxypeptidase B2; D002268:Carboxypeptidases / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013925:Thromboplastin / Q000494:pharmacology; D014018:Tissue Distribution
D000933:Antifibrinolytic Agents; D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; C001650:hippuryl-L-arginine; D013925:Thromboplastin; D001120:Arginine; D002268:Carboxypeptidases; D025901:Carboxypeptidase B2