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Gene Review

F8  -  coagulation factor VIII

Mus musculus

Synonyms: Cf-8, Cf8, Coagulation factor VIII, F8c, FVIII, ...
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Disease relevance of F8

  • Haemophilia A is a classic X-linked disease which affects 1 in 5-10,000 males in all populations and is caused by defects in coagulation factor VIII [1].
  • The live-born rates of normal and FVIII-deficient animals injected in utero with adenovirus murine FVIII (3.3 x 10(5) plaque-forming units) was 87% [2].
  • However, tolerant mice immunized with tetanus toxoid (TT) developed high anti-TT antibody, demonstrating that tolerance is fVIII specific [3].
  • We showed a successful way to generate domain specific anti-FVIII antibodies by using a series of Escherichia coli expressed FVIII fusion peptides [4].
  • Role of coagulation FVIII in septic peritonitis assessed in hemophilic mice [5].

High impact information on F8


Chemical compound and disease context of F8

  • A factor VIII-deficient knockout mouse was used as a model for severe hemophilia A to characterize the immune response to recombinant human factor VIII (fVIII) and to study new approaches for induction of immune tolerance to fVIII [3].
  • To apply this system to hemophilia A inhibitor formation, we created retroviral vectors expressing fVIII amino acids S2173-Y2332 (C2 domain) and S373-R740 (A2 domain) in frame with an IgG heavy chain backbone [9].
  • Factor VIII (fVIII) is the procoagulant plasma glycoprotein that is missing or decreased in hemophilia A [10].
  • Here, we transplanted bone marrow cells transduced with an optimized MSCV-based FVIII oncoretroviral vector into immunocompetent hemophilia A mice that had been conditioned with a potentially lethal dose of irradiation (800 cGy), a sublethal dose of irradiation (550 cGy), or a nonmyeloablative preparative regimen involving busulfan [11].
  • Cells from Lewis lung carcinoma (primary and metastasis), Ehrlich carcinoma ascites and JW sarcoma ascites were able to shorten markedly the recalcification time of normal, Factor VIII- and Factor VII-deficient but not of Factor X-deficient human plasma [12].

Biological context of F8

  • Pulse-field linkage of the P3, G6pd and Cf-8 genes on the mouse X chromosome: demonstration of synteny at the physical level [13].
  • Achievement of high-level (10%-100% of normal) FVIII expression and phenotypic correction required co-injection of an SB transposase-expressing plasmid to facilitate transgene integration in immunotolerized animals [14].
  • We used the Sleeping Beauty (SB) transposon, delivered as naked plasmid DNA by tail-vein injection, to integrate B-domain-deleted FVIII genes into the chromosomes of hemophilia A mice and correct the phenotype [14].
  • Since FVIII protein is a neoantigen to these mice, sustaining therapeutic plasma FVIII levels was problematic due to inhibitory antibody production [14].
  • In the present study, we examined FVIII gene expression in different tissues on a quantitative basis [15].

Anatomical context of F8


Associations of F8 with chemical compounds

  • We have attempted to identify nonhepatocytic sites of fVIII biosynthesis by inducing FHF in mice using acetaminophen overdose, a common cause of human FHF [16].
  • CONCLUSIONS: Despite a higher plasma total cholesterol concentration compared with E degrees mice, E degrees/FVIII degrees mice developed dramatically less early-stage atherosclerotic lesions [18].
  • Receptor-mediated clearance of FVIII is facilitated by heparan sulfate proteoglycans of extracellular matrix, which provide the initial binding of FVIII to the cell surface [19].
  • In vivo neutralization of a C2 domain-specific human anti-Factor VIII inhibitor by an anti-idiotypic antibody [20].
  • We stably expressed in mammalian cells nine active B-domainless human fVIII molecules containing single alanine substitutions at these sites [21].

Physical interactions of F8


Other interactions of F8


Analytical, diagnostic and therapeutic context of F8


  1. Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A. Bi, L., Lawler, A.M., Antonarakis, S.E., High, K.A., Gearhart, J.D., Kazazian, H.H. Nat. Genet. (1995) [Pubmed]
  2. Short-term correction of factor VIII deficiency in a murine model of hemophilia A after delivery of adenovirus murine factor VIII in utero. Lipshutz, G.S., Sarkar, R., Flebbe-Rehwaldt, L., Kazazian, H., Gaensler, K.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. Long-term induction of immune tolerance after blockade of CD40-CD40L interaction in a mouse model of hemophilia A. Rossi, G., Sarkar, J., Scandella, D. Blood (2001) [Pubmed]
  4. Domain specific monoclonal anti-factor VIII antibodies generated by inclusion body-renatured factor VIII peptides. Huang, C.C., Li, L.T., Shen, M.C., Chen, J.Y., Lin, S.W. Thromb. Res. (2001) [Pubmed]
  5. Role of coagulation FVIII in septic peritonitis assessed in hemophilic mice. Schoenmakers, S.H., Brüggemann, L.W., Groot, A.P., Maijs, S., Reitsma, P.H., Spek, C.A. J. Thromb. Haemost. (2005) [Pubmed]
  6. Factor VIII ectopically targeted to platelets is therapeutic in hemophilia A with high-titer inhibitory antibodies. Shi, Q., Wilcox, D.A., Fahs, S.A., Weiler, H., Wells, C.W., Cooley, B.C., Desai, D., Morateck, P.A., Gorski, J., Montgomery, R.R. J. Clin. Invest. (2006) [Pubmed]
  7. In vivo antitumor activity of Sindbis viral vectors. Tseng, J.C., Levin, B., Hirano, T., Yee, H., Pampeno, C., Meruelo, D. J. Natl. Cancer Inst. (2002) [Pubmed]
  8. High-level expression of porcine factor VIII from genetically modified bone marrow-derived stem cells. Gangadharan, B., Parker, E.T., Ide, L.M., Spencer, H.T., Doering, C.B. Blood (2006) [Pubmed]
  9. Induction of tolerance to factor VIII inhibitors by gene therapy with immunodominant A2 and C2 domains presented by B cells as Ig fusion proteins. Lei, T.C., Scott, D.W. Blood (2005) [Pubmed]
  10. Expression of factor VIII by murine liver sinusoidal endothelial cells. Do, H., Healey, J.F., Waller, E.K., Lollar, P. J. Biol. Chem. (1999) [Pubmed]
  11. Correction of murine hemophilia A by hematopoietic stem cell gene therapy. Moayeri, M., Hawley, T.S., Hawley, R.G. Mol. Ther. (2005) [Pubmed]
  12. Evidence that cells from experimental tumours can activate coagulation factor X. Curatolo, L., Colucci, M., Cambini, A.L., Poggi, A., Morasca, L., Donati, M.B., Semeraro, N. Br. J. Cancer (1979) [Pubmed]
  13. Pulse-field linkage of the P3, G6pd and Cf-8 genes on the mouse X chromosome: demonstration of synteny at the physical level. Brockdorff, N., Amar, L.C., Brown, S.D. Nucleic Acids Res. (1989) [Pubmed]
  14. Phenotypic correction and long-term expression of factor VIII in hemophilic mice by immunotolerization and nonviral gene transfer using the Sleeping Beauty transposon system. Ohlfest, J.R., Frandsen, J.L., Fritz, S., Lobitz, P.D., Perkinson, S.G., Clark, K.J., Nelsestuen, G., Key, N.S., McIvor, R.S., Hackett, P.B., Largaespada, D.A. Blood (2005) [Pubmed]
  15. Tissue distribution of factor VIII gene expression in vivo--a closer look. Hollestelle, M.J., Thinnes, T., Crain, K., Stiko, A., Kruijt, J.K., van Berkel, T.J., Loskutoff, D.J., van Mourik, J.A. Thromb. Haemost. (2001) [Pubmed]
  16. Decreased factor VIII levels during acetaminophen-induced murine fulminant hepatic failure. Doering, C.B., Parker, E.T., Nichols, C.E., Lollar, P. Blood (2003) [Pubmed]
  17. Preventing restimulation of memory B cells in hemophilia A: a potential new strategy for the treatment of antibody-dependent immune disorders. Hausl, C., Ahmad, R.U., Schwarz, H.P., Muchitsch, E.M., Turecek, P.L., Dorner, F., Reipert, B.M. Blood (2004) [Pubmed]
  18. Role of the intrinsic coagulation pathway in atherogenesis assessed in hemophilic apolipoprotein E knockout mice. Khallou-Laschet, J., Caligiuri, G., Tupin, E., Gaston, A.T., Poirier, B., Groyer, E., Urbain, D., Maisnier-Patin, S., Sarkar, R., Kaveri, S.V., Lacroix-Desmazes, S., Nicoletti, A. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  19. Receptor-mediated clearance of factor VIII: implications for pharmacokinetic studies in individuals with haemophilia. Saenko, E.L., Ananyeva, N.M. Haemophilia : the official journal of the World Federation of Hemophilia. (2006) [Pubmed]
  20. In vivo neutralization of a C2 domain-specific human anti-Factor VIII inhibitor by an anti-idiotypic antibody. Gilles, J.G., Grailly, S.C., De Maeyer, M., Jacquemin, M.G., VanderElst, L.P., Saint-Remy, J.M. Blood (2004) [Pubmed]
  21. Analysis of the human factor VIII A2 inhibitor epitope by alanine scanning mutagenesis. Lubin, I.M., Healey, J.F., Barrow, R.T., Scandella, D., Lollar, P. J. Biol. Chem. (1997) [Pubmed]
  22. Identification of coagulation factor VIII A2 domain residues forming the binding epitope for low-density lipoprotein receptor-related protein. Sarafanov, A.G., Makogonenko, E.M., Pechik, I.V., Radtke, K.P., Khrenov, A.V., Ananyeva, N.M., Strickland, D.K., Saenko, E.L. Biochemistry (2006) [Pubmed]
  23. Human prostate tumor angiogenesis in nude mice: metalloprotease and plasminogen activator activities during tumor growth and neovascularization of subcutaneously injected matrigel impregnated with human prostate tumor cells. Wilson, M.J., Sinha, A.A. Anat. Rec. (1997) [Pubmed]
  24. Interleukin-17 promotes angiogenesis and tumor growth. Numasaki, M., Fukushi, J., Ono, M., Narula, S.K., Zavodny, P.J., Kudo, T., Robbins, P.D., Tahara, H., Lotze, M.T. Blood (2003) [Pubmed]
  25. Immortal cell lines isolated from heart differentiate to an endothelial cell lineage in the presence of retinoic acid. al Moustafa, A.E., Chalifour, L.E. Cell Growth Differ. (1993) [Pubmed]
  26. Protective immunity induced in mice by F8.1 and F8.2 antigens purified from Schistosoma mansoni eggs. Ferreira, C.C., Santoro, M.M., Goes, A.M. Mem. Inst. Oswaldo Cruz (1998) [Pubmed]
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