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Acta Biologica Hungarica

, Volume 56, Issue 1–2, pp 67–74 | Cite as

Transgenic Mice, Carrying an Expressed Anti-HIV Ribozyme in Their Genome, Show No Sign of Phenotypic Alterations

  • R. L. KatonaEmail author
  • I. Cserpán
  • K. Fátyol
  • Erika Csonka
  • G. Hadlaczky
Article

Abstract

Transgenic mice are suitable model animals for testing the in vivo functionality of custom-tailored ribozymes. Transgenic experiments can demonstrate whether a ribozyme is able to cleave any RNA transcript of the host animal or not. Most probably, this kind of cleavage activity gives rise to phenotypic alterations in mice. In the present paper we demonstrate that an anti-HIV ribozyme does not cause any detectable phenotypic effect in mice carrying and expressing it. Our transgenic mice developed well and were indistinguishable from their wild type counterparts.

Keywords

Transgenic mice ribozyme HIV in vivo model 

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References

  1. 1.
    Beebe, J. A., Fierke, C. A. (1994) A kinetic mechanism for cleavage of precursor tRNA (Asp) catalyzed by the RNA component of Bacillus subtilis ribonuclease P. Biochemistry 33, 10294–10304.CrossRefGoogle Scholar
  2. 2.
    Castanotto, D., Rossi, J. J., Sarver, N. (1994) Antisense catalytic RNAs as therapeutic agents. Adv. Pharmacol. 25, 289–317.CrossRefGoogle Scholar
  3. 3.
    Castanotto, D., Scherr, M., Rossi, J. J. (2000) Intracellular expression and function of antisense catalytic RNAs. Methods Enzymol. 313, 401–420.CrossRefGoogle Scholar
  4. 4.
    Chang, P. S., Cantin, E. M., Zaia, J. A., Ladne, P. A., Stephens, D. A., Sarver, N., Rossi, J. J. (1990) Ribozyme-mediated site-specific cleavage of the HIV-1 genome. Clinical Biotechnology 2, 23–31.Google Scholar
  5. 5.
    Chowrira, B. M., Burke, J. M. (1991) Binding and cleavage of nucleic acids by the “hairpin” ribozyme. Biochemistry 30, 8518–8522.CrossRefGoogle Scholar
  6. 6.
    Diener, T. O. (1991) Subviral pathogens of plants: viroids and viroidlike satellite RNAs. FASEB J. 5, 2808–2813.CrossRefGoogle Scholar
  7. 7.
    Forster, A. C., Symons, R. H. (1987) Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active sites. Cell 49, 211–220.CrossRefGoogle Scholar
  8. 8.
    Guerrier-Takada, C., Altman, S. (2000) Inactivation of gene expression using ribonuclease P and external guide sequences. Methods Enzymol. 313, 442–456.CrossRefGoogle Scholar
  9. 9.
    Hampel, A., Tritz, R., Hicks, M., Cruz, P. (1990) ‘Hairpin’ catalytic RNA model: evidence for helices and sequence requirement for substrate RNA. Nucleic Acids Res. 18, 299–304.CrossRefGoogle Scholar
  10. 10.
    Haseloff, J., Gerlach, W. L. (1988) Simple RNA enzymes with new and highly specific endoribonu-clease activities. Nature 334, 585–591.CrossRefGoogle Scholar
  11. 11.
    Herschlag, D., Cech, T. R. (1990) Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 1. Kinetic description of the reaction of an RNA substrate complementary to the active site. Biochemistry 29, 10159–10171.CrossRefGoogle Scholar
  12. 12.
    Hertel, K. J., Herschlag, D., Uhlenbeck, O. C. (1994) A kinetic and thermodynamic framework for the hammerhead ribozyme reaction. Biochemistry 33, 3374–3385.CrossRefGoogle Scholar
  13. 13.
    Hogan, B., Beddington, R., Costantini, F., Lacy, E. (1994) Manipulating the Mouse Embryo. A Laboratory Manual. Cold Spring Harbor Laboratory Press.Google Scholar
  14. 14.
    Hutchins, C. J., Rathjen, P. D., Forster, A. C., Symons, R. H. (1986) Self-cleavage of plus and minus RNA transcripts of avocado sunblotch viroid. Nucleic Acids Res. 14, 3627–3640.CrossRefGoogle Scholar
  15. 15.
    Locardi, C., Puddu, P., Ferrantini, M., Parlanti, E., Sestili, P., Varano, F., Belardelli, F. (1992) Persistent infection of normal mice with human immunodeficiency virus. J. of Virology 66, 1649–1654.Google Scholar
  16. 16.
    Perrotta, A. T., Been, M. D. (1992) Cleavage of oligoribonucleotides by a ribozyme derived from the hepatitis delta virus RNA sequence. Biochemistry 31, 16–21.CrossRefGoogle Scholar
  17. 17.
    Phylactou, L. A., Darrah, C., Everatt, L., Maniotis, D., Kilpatrick, M. W. (2000) Utilization of properties of natural catalytic RNA to design and synthesize functional ribozymes. Methods Enzymol. 313, 485–506.CrossRefGoogle Scholar
  18. 18.
    Pyle, A. M., Green, J. B. (1994) Building a kinetic framework for group II intron ribozyme activity: quantitation of interdomain binding and reaction rate. Biochemistry 33, 2716–2725.CrossRefGoogle Scholar
  19. 19.
    Roossinck, M. J., Sleat, D., Palukaitis, P. (1992) Satellite RNAs of plant viruses: structures and biological effects. Microbiol. Rev. 56, 265–279.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Sambrook, J., Fritsch, E. F., Maniatis, T. (1989) Molecular Cloning. A laboratory Manual. Cold Spring Harbor Laboratory Press.Google Scholar
  21. 21.
    Sarver, N., Cantin, E. M., Chang, P. S., Zaia, J. A., Ladne, P. A., Stephens, D. A., Rossi, J. J. (1990) Ribozymes as potential anti-HIV-1 therapeutic agents. Science 247, 1222–1225.CrossRefGoogle Scholar
  22. 22.
    Uhlenbeck, O. C. (1987) A small catalytic oligoribonucleotide. Nature 328, 596–600.CrossRefGoogle Scholar
  23. 23.
    Zaug, A. J., Been, M. D., Cech, T. R. (1986) The Tetrahymena ribozyme acts like an RNA restriction endonuclease. Nature 324, 429–433.CrossRefGoogle Scholar

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© Akadémiai Kiadó, Budapest 2005

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • R. L. Katona
    • 1
    Email author
  • I. Cserpán
    • 1
  • K. Fátyol
    • 1
  • Erika Csonka
    • 1
  • G. Hadlaczky
    • 1
  1. 1.Institute of Genetics, Biological Research CenterHungarian Academy of SciencesSzegedHungary

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