A murine model of factor XI deficiency

D. Gailani, N. M. Lasky, G. J. Broze

Research output: Contribution to journalArticle

104 Scopus citations

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.

Original languageEnglish
Pages (from-to)134-144
Number of pages11
JournalBlood Coagulation and Fibrinolysis
Volume8
Issue number2
DOIs
StatePublished - Jan 1 1997

Keywords

  • animal
  • blood coagulation disorders
  • disease models
  • factor XI

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