title: A murine model of factor XI deficiency.
abstract: To facilitate investigations into the physiologic and pathologic roles of factor XI, we have developed a murine model of severe factor XI deficiency using the technique of homologous recombination in embryonic stem cells. The factor XI gene was disrupted by introducing a neomycin phosphotransferase gene into the fifth exon. The activated partial thromboplastin times of homozygous null mice were prolonged (158- > 200 s) compared with wild type (25-34 s) and heterozygous null (40-61 s) litter mates. Factor XI activity was absent from the plasma of mice homozygous for the null mutation and factor XI mRNA was undetectable by Northern blot and reverse transcription/PCR in the livers of homozygous null animals. The genotypes of progeny from matings of mice heterozygous for the factor XI null allele followed the expected Mendelian ratio (1:2:1, wild type 26%, heterozygote null 54%, homozygous null 20%), indicating that severe factor XI deficiency did not result in increased intrauterine death. Results of a tail transection bleeding time assay were similar for wild type and homozygous null animals with, at most, a tendency for slightly prolonged bleeding in the homozygous null animals. The factor XI deficient mice are a unique tool for evaluating the role of factor XI in normal hemostasis and pathologic coagulation.
authors.affiliation: Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232-6305, USA.
authors.forename: D
authors.initials: D
authors.lastname: Gailani
authors.forename: N M
authors.initials: NM
authors.lastname: Lasky
authors.forename: G J
authors.initials: GJ
authors.lastname: Broze
mesh_terms: D000818:Animals; D001760:Bleeding Time; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005172:Factor XI / Q000235:genetics; D005173:Factor XI Deficiency / Q000503:physiopathology*; D018390:Gene Targeting; D008099:Liver / Q000737:chemistry; D051379:Mice; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D012333:RNA, Messenger / Q000032:analysis; D013234:Stem Cells / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D005172:Factor XI