Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research News and Views
  • Published:

The right time and place for molecular scissors

Nature Biotechnology volume 17, pages 1062–1063 (1999)Cite this article

The development of genetic tools has been and will continue to be a driving force in biological discovery. In particular, the ability to mutate genes within the mouse genome has been instrumental in the identification and understanding of genetic pathways controlling organogenesis and tumorigenesis. Now, Wen-Hwa Lee and colleagues1 report experiments that take the application of molecular tools to new heights. They combined the generic Cre-loxP recombination system with a tetracycline-dependent switch and topped it off with tissue-specific control elements. This technical voyage will enable biologists to precisely manipulate individual genes in specific tissues and at predetermined time points.

What are the fundamentals of advanced gene switches? During the past decade engineers in many molecular workshops around the world have searched through the tool boxes of prokaryotes and turned up gadgets and gismos that greatly aided molecular engineers in manipulating the mouse genome with an ever-increasing sophistication. Included in our repertoire are the tools of homologous recombination that were developed by the groups of Smithies2 and Capecchi3, the Cre-loxP recombination system developed by Sternberg4 (originally isolated from the bacteriophage P1), and the tetracycline control switch developed by Bujard5 (composed of components of the bacterial tetracycline repressor and the herpesvirus transcription element VP16). Lastly, DNA control elements that have the capacity to direct gene expression to specific cell types have been identified over the past decade.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Strategy for the deletion of genes from specific cell types at defined time points.

References

  1. Utomo, A.R.H., Nikitin, A.Y. & Lee, W.-H. Nat. Biotechnol. 17, 1091– 1096 (1999).

    Article  CAS  Google Scholar 

  2. Doetschman, T. et al. Nature 330, 576–578 (1987).

    Article  CAS  Google Scholar 

  3. Thomas, K.R., Folger, K.R. & Capecchi, M.R. Cell 44, 419– 428.

  4. Sternberg, N. & Hamilton, D. J Mol Biol 150, 467–486 (1981).

    Article  CAS  Google Scholar 

  5. Gossen, M. & Bujard, H. Proc. Natl. Acad. Sci. USA 89, 5547–5551 (1992).

    Article  CAS  Google Scholar 

  6. Xu, X. et al. Nature Genetics 22, 37–43 (1999).

    Article  CAS  Google Scholar 

  7. Ewald, D. et al. Science 273, 1384–1386 (1996).

    Article  CAS  Google Scholar 

  8. Furth, P.A. et al. Proc. Natl. Acad. Sci. U.S.A. 91, 9302– 9306 (1994).

    Article  CAS  Google Scholar 

  9. St-Onge, L., Furth, P.A. & Gruss, P. Nucleic Acids Res 24, 3875– 3877 (1996).

    Article  CAS  Google Scholar 

  10. Gossen, M. et al. Science 268, 1766–1769 (1995).

    Article  CAS  Google Scholar 

  11. Gordon, K. et al. Bio/technology 5, 1183–1187 (1987).

    CAS  Google Scholar 

  12. Wagner, K.-U. et al. Nucleic Acids Res. 25, 4323– 4324 (1987).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. cheif of the laboratory of Genetics and Physiology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bldg. 8, Rm. 101, Bethesda, 20892, MD

    Lothar Hennighausen

  2. associate professor of medicine and physiology at the departments of medicine and physiology, Institute of Human Virology, University of Maryland Medical School, 725 West Lombard Street, Room 545, Baltimore, 21201-1192, MD

    Priscilla A. Furth

Authors
  1. Lothar Hennighausen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Priscilla A. Furth
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hennighausen, L., Furth, P. The right time and place for molecular scissors. Nat Biotechnol 17, 1062–1063 (1999). https://doi.org/10.1038/15046

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/15046

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing