Gene targeting in hemostasis. tissue factor pathway inhibitor.
Tissue Factor Pathway Inhibitor (TFPI) is a serine protease inhibitor of the Factor VIIa/Tissue Factor (FVIIa/TF)-initiated clotting cascade. Mice expressing a mutant form of TFPI, in which its Kunitz-1 domain has been deleted (TFPIKu1delta/delta), die prematurely in embryogenesis between E9.5dpc and birth. These results provide a rationale for the absence of TFPI-deficient patients. This early mortality can be ameliorated by an accompanying heterozygous or homozygous deficiency in FVII. Thus, diminishment of FVII activity precludes the requirement for TFPI-mediated inhibition of the FVIIa/TF pathway during embryogenesis.
Chan
J C
JC
251 Nieuwland Science Hall, W.M. Keck Center for Transgene Research and the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, USA. chan.8@nd.edu
D000818:Animals; D000831:Animals, Newborn; D020147:Coagulation Protein Disorders / Q000196:embryology; D005167:Factor VII / Q000235:genetics / Q000378:metabolism; D005168:Factor VII Deficiency / Q000196:embryology / Q000235:genetics; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018390:Gene Targeting; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008074:Lipoproteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D015842:Serine Proteinase Inhibitors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
D008074:Lipoproteins; D015842:Serine Proteinase Inhibitors; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII; D005340:Fibrinogen