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Gene Review

F7  -  coagulation factor VII

Mus musculus

Synonyms: AI132620, Cf7, Coagulation factor VII, FVII, Serum prothrombin conversion accelerator, ...
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Disease relevance of F7

  • In contrast, FVII deficiency is not embryonic lethal, but FVII-/- neonates died from hemorrhage within the first days after birth [1].
  • Here, we report a novel treatment strategy with a recombinant adeno-associated virus vector delivering a modified FVII transgene that can be intracellularly processed and secreted as activated FVII (FVIIa) [2].
  • The efficacy and safety of an immunoconjugate (icon) molecule, composed of a mutated mouse factor VII (mfVII) targeting domain and the Fc effector domain of an IgG1 Ig (mfVII/Fc icon), was tested with a severe combined immunodeficient (SCID) mouse model of human prostatic cancer and an immunocompetent mouse model of mouse prostatic cancer [3].
  • Mice expressing low levels of murine FVII ( approximately 1% of wild-type levels) exhibited a similar pattern of hemosiderin deposition and fibrosis in their hearts [4].
  • The immunotherapy tests in SCID mice demonstrated that intratumoral injections of the adenoviral vector encoding the mfVII/human Fc icon resulted in long-term regression of the injected human prostatic tumor and also of a distant uninjected tumor, without associated toxicity to the mice [3].

High impact information on F7

  • Blood coagulation in vivo is initiated by factor VII (FVII) binding to its cellular receptor tissue factor (TF) [5].
  • FVII-/- mice succumbed perinatally because of fatal haemorrhaging from normal blood vessels [5].
  • FVII(-/-)/PC(-/-) embryos, although present at their expected Mendelian frequency, displayed a phenotype that had not been observed in either the FVII or PC singly deficient embryos [6].
  • To investigate the role of TF in embryogenesis, we made mutant hTF minigenes whose products either bound FVII/VIIa at a reduced level or lacked the cytoplasmic domain [7].
  • Thus, the rescue of TFPIdelta/delta embryos, either by an accompanying homozygous or heterozygous FVII deficiency, suggests that diminishment of FVII activity precludes the need for TFPI-mediated inhibition of the FVIIa/tissue factor coagulation pathway during embryogenesis [8].

Biological context of F7


Anatomical context of F7

  • The construct conferring highest in vitro FVIII secretion was electroporated into skeletal muscle of FVII null mice in vivo for phenotypic correction using a protocol that minimised tissue injury [13].
  • RESULTS: Morphological analysis of the joints 4 days after TF/FVII injection revealed influx of CD4-Mac1+ mononuclear leukocytes into synovial tissue followed by cartilage and bone destruction [14].
  • Interaction between macrophages and lymphocytes in sustaining joint inflammation was proved by the requirement of the combined lymphocyte/ monocyte depletion to abolish TF/FVII induced arthritis [14].
  • Interestingly, TF/FVII complexes were detected in synovial fluid of 20/40 patients with RA [14].

Associations of F7 with chemical compounds

  • Thus, the potential protective effects in vivo of a genetic-based reduction in FVII levels have been investigated in a murine model of acute inflammation, namely lipopolysaccharide (LPS)-induced lethal endotoxaemia [15].
  • The expression of the FVII construct was tested in a C2 cell culture system and also when injected directly into mouse muscle [16].
  • Murine FVII was activated to FVIIa with human factor Xa and upon reaction with FFR-chloromethyl ketone converted into an active site-blocked TF antagonist, FFR-FVIIa [17].
  • Two proteins, FI and FVII, have been purified from a whole worm extract of adult Ascaris suum, using ammonium sulfate precipitation, Sephadex gel filtration and DEAE cellulose chromatography [18].
  • BACKGROUND AND OBJECTIVES: Arginine 315 in factor VII (FVII) belongs to a solvent-exposed loop involved in direct interaction with the co-factor (tissue factor, TF), in transmission of TF-induced effects and potentially in FVIIa inactivation [19].

Other interactions of F7

  • This resulted in a TF- and FVII-dependent FXa and thrombin generation as measured in the effluent at the outlet of the system [20].

Analytical, diagnostic and therapeutic context of F7

  • FVII antigen in media was estimated by immunoassay while FVII activity was assessed by prothrombin-time based and FXa generation assays [19].


  1. Gene targeting of tissue factor, factor X, and factor VII in mice: their involvement in embryonic development. Aasrum, M., Prydz, H. Biochemistry Mosc. (2002) [Pubmed]
  2. Novel therapeutic approach for hemophilia using gene delivery of an engineered secreted activated Factor VII. Margaritis, P., Arruda, V.R., Aljamali, M., Camire, R.M., Schlachterman, A., High, K.A. J. Clin. Invest. (2004) [Pubmed]
  3. Targeting tissue factor on tumor vascular endothelial cells and tumor cells for immunotherapy in mouse models of prostatic cancer. Hu, Z., Garen, A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. Tissue factor deficiency causes cardiac fibrosis and left ventricular dysfunction. Pawlinski, R., Fernandes, A., Kehrle, B., Pedersen, B., Parry, G., Erlich, J., Pyo, R., Gutstein, D., Zhang, J., Castellino, F., Melis, E., Carmeliet, P., Baretton, G., Luther, T., Taubman, M., Rosen, E., Mackman, N. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. Mice lacking factor VII develop normally but suffer fatal perinatal bleeding. Rosen, E.D., Chan, J.C., Idusogie, E., Clotman, F., Vlasuk, G., Luther, T., Jalbert, L.R., Albrecht, S., Zhong, L., Lissens, A., Schoonjans, L., Moons, L., Collen, D., Castellino, F.J., Carmeliet, P. Nature (1997) [Pubmed]
  6. Combined factor VII/protein C deficiency results in intrauterine coagulopathy in mice. Chan, J.C., Cornelissen, I., Collen, D., Ploplis, V.A., Castellino, F.J. J. Clin. Invest. (2000) [Pubmed]
  7. Mouse embryogenesis requires the tissue factor extracellular domain but not the cytoplasmic domain. Parry, G.C., Mackman, N. J. Clin. Invest. (2000) [Pubmed]
  8. Factor VII deficiency rescues the intrauterine lethality in mice associated with a tissue factor pathway inhibitor deficit. Chan, J.C., Carmeliet, P., Moons, L., Rosen, E.D., Huang, Z.F., Broze, G.J., Collen, D., Castellino, F.J. J. Clin. Invest. (1999) [Pubmed]
  9. Daily and circadian rhythms of tissue factor pathway inhibitor and factor VII activity. Pinotti, M., Bertolucci, C., Portaluppi, F., Colognesi, I., Frigato, E., Foà, A., Bernardi, F. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  10. Characterization of transcriptional regulatory elements in the promoter region of the murine blood coagulation factor VII gene. Stauffer, D.R., Chukwumezie, B.N., Wilberding, J.A., Rosen, E.D., Castellino, F.J. J. Biol. Chem. (1998) [Pubmed]
  11. Characterization of a cDNA encoding murine coagulation factor VII. Idusogie, E., Rosen, E., Geng, J.P., Carmeliet, P., Collen, D., Castellino, F.J. Thromb. Haemost. (1996) [Pubmed]
  12. Gene targeting in hemostasis. Factor VII. Chan, J.C. Front. Biosci. (2001) [Pubmed]
  13. FVIII gene delivery by muscle electroporation corrects murine hemophilia A. Long, Y.C., Jaichandran, S., Ho, L.P., Tien, S.L., Tan, S.Y., Kon, O.L. The journal of gene medicine. (2005) [Pubmed]
  14. Intra-articular tissue factor/factor VII complex induces chronic arthritis. Bokarewa, M.I., Morrissey, J., Tarkowski, A. Inflamm. Res. (2002) [Pubmed]
  15. A coagulation factor VII deficiency protects against acute inflammatory responses in mice. Xu, H., Ploplis, V., Castellino, F. J. Pathol. (2006) [Pubmed]
  16. Expression of factor VII by muscle cells in vitro and in vivo following direct gene transfer: modelling gene therapy for haemophilia. Miller, G., Steinbrecher, R.A., Murdock, P.J., Tuddenham, E.G., Lee, C.A., Pasi, K.J., Goldspink, G. Gene Ther. (1995) [Pubmed]
  17. Characterization of recombinant murine factor VIIa and recombinant murine tissue factor: a human-murine species compatibility study. Petersen, L.C., Nørby, P.L., Branner, S., Sørensen, B.B., Elm, T., Stennicke, H.R., Persson, E., Bjørn, S.E. Thromb. Res. (2005) [Pubmed]
  18. Purification and characterisation of two proteins from Ascaris suum extract, antigenically different but bearing common allergenic epitopes. Dandeu, J.P., Lux, M. Immunol. Commun. (1978) [Pubmed]
  19. Characterization of mild coagulation factor VII deficiency: activity and clearance of the Arg315Trp and Arg315Lys variants in the Cys310-Cys329 loop (c170s). Furlan Freguia, C., Toso, R., Pollak, E.S., Arruda, V.R., Pinotti, M., Bernardi, F. Haematologica (2004) [Pubmed]
  20. Activated factor X and thrombin formation triggered by tissue factor on endothelial cell matrix in a flow model: effect of the tissue factor pathway inhibitor. van 't Veer, C., Hackeng, T.M., Delahaye, C., Sixma, J.J., Bouma, B.N. Blood (1994) [Pubmed]
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