A murine model of factor XI deficiency : Blood Coagulation & Fibrinolysis (original) (raw)
Review Paper: PDF Only
D. Gailani is from the Department of Pathology and Division of Hematology, Vanderbilt University School of Medicine, 547 MRB II, 2220 Pierce Avenue, Nashville, TN 37232–6305, USA. N. M. Lasky and G. J. Broze Jr are with the Division of Hematology, Jewish Hospital at Washington University School of Medicine, 216 S. Kingshighway Blvd, St Louis, MO 63110, USA. Address correspondence to: G. J. Broze Jr. Tel: (+1) 314 362–8811; Fax: (+1) 314 362–8813.
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.
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