title: Gene targeting in hemostasis. factor XI.
abstract: Factor XI (FXI) is the zymogen of a plasma serine protease (FXIa) that contributes to hemostasis by activating factor IX (FIX). This reaction appears to be important for sustaining thrombin production after initial fibrin formation, to consolidate and protect fibrin clots from degradation by fibrinolysis. Humans with congenital FXI deficiency have a variable propensity to bleed after trauma or surgery, but do not experience the "spontaneous" hemorrhage in joints and soft tissue characteristic of hemophilia (FVIII or FIX deficiency). Mice homozygous for a disruption of the FXI gene (FXI-/-) have prolonged activated partial thromboplastin times and no detectable plasma FXI activity. Like their human counterparts, FXI-/- animals are generally healthy, reproduce normally, and do not develop spontaneous hemorrhage. In tail bleeding time assays, FXI-/- animals may have slightly prolonged bleeding compared to FXI+/+ and FXI+/- animals, however, a consistent hemostatic deficit has not been identified. More impressive results are obtained when FXI-/- mice are crossed with protein C deficient mice. Severe FXI deficiency partially ameliorates the devastating hypercoagulable state associated with severe protein C deficiency, indicating that FXI plays a role in certain thrombotic conditions.
authors.affiliation: Departments of Pathology and Medicine, Vanderbilt University, Nashville, TN, USA. Dave.Gailani@mcmail.vanderbilt.edu
authors.forename: D
authors.initials: D
authors.lastname: Gailani
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002318:Cardiovascular Diseases / Q000503:physiopathology; D005172:Factor XI / Q000235:genetics* / Q000502:physiology; D005173:Factor XI Deficiency / Q000196:embryology / Q000503:physiopathology; D018390:Gene Targeting; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D009154:Mutation; D010641:Phenotype
chemical_list: D005172:Factor XI