A total fibrinogen deficiency is compatible with the development of pulmonary fibrosis in mice

Am J Pathol. 2000 Sep;157(3):703-8. doi: 10.1016/S0002-9440(10)64582-8.


In addition to their well-known roles in hemostasis, fibrinogen (Fg) and fibrin (Fn) have been implicated in a number of other physiological and pathophysiological events. One of these involves the fibroproliferative response after acute lung injury, which is the focus of the current study. Mice with a total Fg deficiency (FG(-/-)) were generated by breeding heterozygous (FG(+/-)) pairs, each of which contained an allele with a targeted deletion of its Fg-gamma-chain gene. The resulting FG(-/-) animals did not possess detectable plasma Fg. FG(-/-) mice were then used to assess the roles of Fg and Fn in a bleomycin-induced acute lung injury model. Intratracheal administration of bleomycin in wild-type and FG(-/-) mice resulted in equivalent deposition of interstitial collagen and fibrotic lesions at days 7 and 14 after administration. This indicates that Fg and/or Fn are not essential for the development of bleomycin-induced pulmonary fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Afibrinogenemia / genetics*
  • Afibrinogenemia / metabolism
  • Afibrinogenemia / pathology
  • Animals
  • Bleomycin
  • Collagen / metabolism
  • DNA / analysis
  • Disease Models, Animal
  • Female
  • Fibrinogen / genetics*
  • Fibrinogen / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Gene Targeting
  • Heterozygote
  • Homozygote
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Polymerase Chain Reaction
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / genetics*
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology


  • fibrinopeptides gamma
  • Bleomycin
  • Fibrinogen
  • Collagen
  • DNA