Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jul;87(13):5173–5177. doi: 10.1073/pnas.87.13.5173

Phenotypic correction of factor IX deficiency in skin fibroblasts of hemophilic dogs.

J H Axelrod 1, M S Read 1, K M Brinkhous 1, I M Verma 1
PMCID: PMC54284  PMID: 2367529

Abstract

Primary skin fibroblasts from hemophilic dogs were transduced by recombinant retrovirus (LNCdF9L) containing a canine factor IX cDNA. High levels of biologically active canine factor IX (1.0 micrograms per 10(6) cells per 24 hr) were secreted in the medium. The level of factor IX produced increased substantially if the cells were stimulated by basic fibroblast growth factor during infection. Additionally, we also report that endothelial cells transduced by this virus can produce high levels of biologically active factor IX. We propose that skin fibroblasts and endothelial cells from hemophilia B dogs may serve as potential venues for the development and testing of models for treatment of hemophilia B by retrovirally mediated gene replacement therapy.

Full text

PDF
5173

Images in this article

5175Image
on p.5175
5176Image
on p.5176

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anson D. S., Choo K. H., Rees D. J., Giannelli F., Gould K., Huddleston J. A., Brownlee G. G. The gene structure of human anti-haemophilic factor IX. EMBO J. 1984 May;3(5):1053–1060. doi: 10.1002/j.1460-2075.1984.tb01926.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anson D. S., Hock R. A., Austen D., Smith K. J., Brownlee G. G., Verma I. M., Miller A. D. Towards gene therapy for hemophilia B. Mol Biol Med. 1987 Feb;4(1):11–20. [PubMed] [Google Scholar]
  3. Bajaj S. P., Rapaport S. I., Maki S. L. A monoclonal antibody to factor IX that inhibits the factor VIII:Ca potentiation of factor X activation. J Biol Chem. 1985 Sep 25;260(21):11574–11580. [PubMed] [Google Scholar]
  4. Bender M. A., Palmer T. D., Gelinas R. E., Miller A. D. Evidence that the packaging signal of Moloney murine leukemia virus extends into the gag region. J Virol. 1987 May;61(5):1639–1646. doi: 10.1128/jvi.61.5.1639-1646.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bos E. S., van der Doelen A. A., van Rooy N., Schuurs A. H. 3,3',5,5' - Tetramethylbenzidine as an Ames test negative chromogen for horse-radish peroxidase in enzyme-immunoassay. J Immunoassay. 1981;2(3-4):187–204. doi: 10.1080/15321818108056977. [DOI] [PubMed] [Google Scholar]
  6. Brinkhous K. M., Davis P. D., Graham J. B., Dodds W. J. Expression and linkage of genes for X-linked hemophilias A and B in the dog. Blood. 1973 Apr;41(4):577–585. [PubMed] [Google Scholar]
  7. Burgess W. H., Maciag T. The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem. 1989;58:575–606. doi: 10.1146/annurev.bi.58.070189.003043. [DOI] [PubMed] [Google Scholar]
  8. Danos O., Mulligan R. C. Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6460–6464. doi: 10.1073/pnas.85.17.6460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Evans J. P., Brinkhous K. M., Brayer G. D., Reisner H. M., High K. A. Canine hemophilia B resulting from a point mutation with unusual consequences. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10095–10099. doi: 10.1073/pnas.86.24.10095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Evans J. P., Watzke H. H., Ware J. L., Stafford D. W., High K. A. Molecular cloning of a cDNA encoding canine factor IX. Blood. 1989 Jul;74(1):207–212. [PubMed] [Google Scholar]
  11. Fujikawa K., Davie E. W. Bovine factor IX (Christmas factor). Methods Enzymol. 1976;45:74–83. doi: 10.1016/s0076-6879(76)45011-5. [DOI] [PubMed] [Google Scholar]
  12. Goldsmith J. C., Chung K. S., Roberts H. R. A simple assay for human factor IX: use of canine hemophilia B plasma as substrate. Thromb Res. 1978 Mar;12(3):497–502. doi: 10.1016/0049-3848(78)90320-1. [DOI] [PubMed] [Google Scholar]
  13. Kaplan P. L., Simon S., Cartwright C. A., Eckhart W. cDNA cloning with a retrovirus expression vector: generation of a pp60c-src cDNA clone. J Virol. 1987 May;61(5):1731–1734. doi: 10.1128/jvi.61.5.1731-1734.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Li C. L., Dwarki V. J., Verma I. M. Expression of human alpha-globin and mouse/human hybrid beta-globin genes in murine hemopoietic stem cells transduced by recombinant retroviruses. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4349–4353. doi: 10.1073/pnas.87.11.4349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Markowitz D., Goff S., Bank A. A safe packaging line for gene transfer: separating viral genes on two different plasmids. J Virol. 1988 Apr;62(4):1120–1124. doi: 10.1128/jvi.62.4.1120-1124.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miller A. D., Buttimore C. Redesign of retrovirus packaging cell lines to avoid recombination leading to helper virus production. Mol Cell Biol. 1986 Aug;6(8):2895–2902. doi: 10.1128/mcb.6.8.2895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nabel E. G., Plautz G., Boyce F. M., Stanley J. C., Nabel G. J. Recombinant gene expression in vivo within endothelial cells of the arterial wall. Science. 1989 Jun 16;244(4910):1342–1344. doi: 10.1126/science.2499928. [DOI] [PubMed] [Google Scholar]
  18. Nelson J. A., Reynolds-Kohler C., Smith B. A. Negative and positive regulation by a short segment in the 5'-flanking region of the human cytomegalovirus major immediate-early gene. Mol Cell Biol. 1987 Nov;7(11):4125–4129. doi: 10.1128/mcb.7.11.4125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Palmer T. D., Thompson A. R., Miller A. D. Production of human factor IX in animals by genetically modified skin fibroblasts: potential therapy for hemophilia B. Blood. 1989 Feb;73(2):438–445. [PubMed] [Google Scholar]
  20. Remy J. C., Fruchter R. G., Boyce J., Macasaet M., Choi K., Rotman M. Complications of combined surgery and radiation therapy for carcinoma of the endometrium. Int J Gynaecol Obstet. 1985 Apr;23(2):83–93. doi: 10.1016/0020-7292(85)90049-9. [DOI] [PubMed] [Google Scholar]
  21. St Louis D., Verma I. M. An alternative approach to somatic cell gene therapy. Proc Natl Acad Sci U S A. 1988 May;85(9):3150–3154. doi: 10.1073/pnas.85.9.3150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. White G. C., 2nd, Blatt P. M., McMillan C. W., Webster W. P., Lesesne H. R., Roberts H. R. Medical complications of hemophilia. South Med J. 1980 Feb;73(2):155–160. doi: 10.1097/00007611-198002000-00011. [DOI] [PubMed] [Google Scholar]
  23. White G. C., 2nd, Roberts H. R., Kingdon H. S., Lundblad R. L. Prothrombin complex concentrates: potentially thrombogenic materials and clues to the mechanism of thrombosis in vivo. Blood. 1977 Feb;49(2):159–170. [PubMed] [Google Scholar]
  24. Wilson J. M., Birinyi L. K., Salomon R. N., Libby P., Callow A. D., Mulligan R. C. Implantation of vascular grafts lined with genetically modified endothelial cells. Science. 1989 Jun 16;244(4910):1344–1346. doi: 10.1126/science.2734614. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES