Sustained somatic gene inactivation by viral transfer of Cre recombinase

Astrid Rohlmann, Michael Gotthardt, Thomas E. Willnow, Robert E Hammer, Joachim Herz

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Transgenic and knockout mice have proven invaluable tools for analyzing physiologically relevant functions of numerous genes. In some cases, however, pleiotropic effects that result from a variable requirement for a particular gene in different tissues, cell types, or stages of embryonic development may complicate the analysis due to a complex phenotype or embryonic lethality. The IoxP/Cre-mediated recombination system, which allows tissue-specific gene targeting in the mouse, can be used to overcome these problems. A limitation of current methods is that a mouse carrying a IoxP-tagged gene must be crossed with a transgenic mouse expressing the Cre recombinase in an appropriate tissue to obtain the desired gene rearrangement. We have used recombinant adenovirus carrying the Cre recombinase to induce virtually quantitative somatic cell gene disruption in the liver. The targeted gene was the multifunctional low-density lipoprotein receptor-related protein (LRP), a cell surface receptor for α2-macroglobulin and other ligands. Transient expression of Cre following adenoviral infection produced the predicted gene rearrangement, functionally inactivating LRP in the liver. Rearrangement occurred within 6 days after infection and remained stable for at least 28 days. The results demonstrate the suitability of adenoviral Cre gene transfer to induce long-term, quantitative, and temporally controlled gene disruption in the mouse.

Original languageEnglish (US)
Pages (from-to)1562-1565
Number of pages4
JournalNature Biotechnology
Volume14
Issue number11
StatePublished - Nov 1996

Fingerprint

Gene Silencing
Genes
Gene Rearrangement
Lipoproteins
Transgenic Mice
Tissue
LDL-Receptor Related Proteins
Liver
Lipoprotein Receptors
Macroglobulins
Gene Targeting
LDL Receptors
Cell Surface Receptors
Proteins
Gene transfer
Infection
Cre recombinase
Adenoviridae
Knockout Mice
Genetic Recombination

Keywords

  • adenovirus
  • homologous recombination
  • LRP
  • protease

ASJC Scopus subject areas

  • Microbiology

Cite this

Sustained somatic gene inactivation by viral transfer of Cre recombinase. / Rohlmann, Astrid; Gotthardt, Michael; Willnow, Thomas E.; Hammer, Robert E; Herz, Joachim.

In: Nature Biotechnology, Vol. 14, No. 11, 11.1996, p. 1562-1565.

Research output: Contribution to journalArticle

Rohlmann, A, Gotthardt, M, Willnow, TE, Hammer, RE & Herz, J 1996, 'Sustained somatic gene inactivation by viral transfer of Cre recombinase', Nature Biotechnology, vol. 14, no. 11, pp. 1562-1565.
Rohlmann, Astrid ; Gotthardt, Michael ; Willnow, Thomas E. ; Hammer, Robert E ; Herz, Joachim. / Sustained somatic gene inactivation by viral transfer of Cre recombinase. In: Nature Biotechnology. 1996 ; Vol. 14, No. 11. pp. 1562-1565.
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