Cited by 106CRISPR and Genetic EngineeringAnimal Genetics and ReproductionVirus-based gene therapy research

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Site-Specific Recombinases for Manipulation of the Mouse Genome

Open access
Birling, Marie-Christine, Gofflot, Françoise, Warot, Xavier·2009·Methods in Molecular Biology

Abstract

Site-specific recombination systems are widespread and popular tools for all scientists interested in manipulating the mouse genome. In this chapter, we focus on the use of site-specific recombinases (SSR) to unravel the function of genes of the mouse. In the first part, we review the most commonly used SSR, Cre and Flp, as well as the newly developed systems such as Dre and PhiC31, and we present the inducible SSR systems. As experience has shown that these systems are not as straightforward as expected, particular attention is paid to facts and artefacts associated with their production and applications to study the mouse genome. In the next part of this chapter, we illustrate new applications of SSRs that allow engineering of the mouse genome with more and more precision, including the FLEX and the RMCE strategies. We conclude and suggest a workflow procedure that can be followed when using SSR to create your mouse model of interest. Together, these strategies and procedures provide the basis for a wide variety of studies that will ultimately lead to the analysis of the function of a gene at the cellular level in the mouse.

Overview

Integrity signals

Registry

Crossref · 10.1007/978-1-60327-019-9_16

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 2 references

Research works printed but not linked: 62

  1. Grindley, N.D., Whiteson, K.L. and Rice, P.A. (2006) Mechanisms of site-specific recombination. Annu Rev Biochem, 75, 567–605 · DOI
  2. Sauer, B. and Henderson, N. (1988) Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci U S A, 85, 5166–5170 · DOI · Paper page
  3. Metzger, D. and Chambon, P. (2001) Site- and time-specific gene targeting in the mouse. Methods, 24, 71–80 · DOI
  4. Nagy, A. (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis, 26, 99–109 · DOI
  5. Branda, C.S. and Dymecki, S.M. (2004) Talking about a revolution: the impact of site-specific recombinases on genetic analyses in mice. Dev Cell, 6, 7–28 · DOI
  6. Sauer, B. and Henderson, N. (1989) Cre-stimulated recombination at loxP-containing DNA sequences placed into the mammalian genome. Nucleic Acids Res, 17, 147–161 · DOI
  7. Gu, H., Marth, J.D., Orban, P.C., Mossmann, H. and Rajewsky, K. (1994) Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science, 265, 103–106 · DOI
  8. Lakso, M., Sauer, B., Mosinger, B., Jr., Lee, E.J., Manning, R.W., Yu, S.H., Mulder, K.L. and Westphal, H. (1992) Targeted oncogene activation by site-specific recombination in transgenic mice. Proc Natl Acad Sci U S A, 89, 6232–6236 · DOI
  9. Orban, P.C., Chui, D. and Marth, J.D. (1992) Tissue- and site-specific DNA recombination in transgenic mice. Proc Natl Acad Sci U S A, 89, 6861–6865 · DOI
  10. Dupe, V., Davenne, M., Brocard, J., Dolle, P., Mark, M., Dierich, A., Chambon, P. and Rijli, F.M. (1997) In vivo functional analysis of the Hoxa-1 3′ retinoic acid response element (3′RARE). Development, 124, 399–410 · DOI
  11. Gaveriaux-Ruff, C. and Kieffer, B.L. (2007) Conditional gene targeting in the mouse nervous system: insights into brain function and diseases. Pharmacol Ther, 113, 619–634 · DOI
  12. O’Gorman, S., Fox, D.T. and Wahl, G.M. (1991) Recombinase-mediated gene activation and site-specific integration in mammalian cells. Science, 251, 1351–1355 · DOI
  13. Buchholz, F., Angrand, P.O. and Stewart, A.F. (1998) Improved properties of FLP recombinase evolved by cycling mutagenesis. Nat Biotechnol, 16, 657–662 · DOI
  14. Raymond, C.S. and Soriano, P. (2007) High-efficiency FLP and PhiC31 site-specific recombination in mammalian cells. PLoS ONE, 2, e162 · DOI
  15. Farley, F.W., Soriano, P., Steffen, L.S. and Dymecki, S.M. (2000) Widespread recombinase expression using FLPeR (flipper) mice. Genesis, 28, 106–110 · DOI
  16. Kanki, H., Suzuki, H. and Itohara, S. (2006) High-efficiency CAG-FLPe deleter mice in C57 BL/6J background. Exp Anim, 55, 137–141 · DOI
  17. Rodriguez, C.I., Buchholz, F., Galloway, J., Sequerra, R., Kasper, J., Ayala, R., Stewart, A.F. and Dymecki, S.M. (2000) High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet, 25, 139–140 · DOI
  18. Sauer, B. and McDermott, J. (2004) DNA recombination with a heterospecific Cre homolog identified from comparison of the pac-c1 regions of P1-related phages. Nucleic Acids Res, 32, 6086–6095 · DOI
  19. Thorpe, H.M. and Smith, M.C. (1998) In vitro site-specific integration of bacteriophage DNA catalyzed by a recombinase of the resolvase/invertase family. Proc Natl Acad Sci U S A, 95, 5505–5510 · DOI
  20. Belteki, G., Gertsenstein, M., Ow, D.W. and Nagy, A. (2003) Site-specific cassette exchange and germline transmission with mouse ES cells expressing phiC31 integrase. Nat Biotechnol, 21, 321–324 · DOI
  21. Sclimenti, C.R., Thyagarajan, B. and Calos, M.P. (2001) Directed evolution of a recombinase for improved genomic integration at a native human sequence. Nucleic Acids Res, 29, 5044–5051 · DOI
  22. Andreas, S., Schwenk, F., Kuter-Luks, B., Faust, N. and Kuhn, R. (2002) Enhanced efficiency through nuclear localization signal fusion on phage PhiC31-integrase: activity comparison with Cre and FLPe recombinase in mammalian cells. Nucleic Acids Res, 30, 2299–2306 · DOI
  23. Kuhn, R., Schwenk, F., Aguet, M. and Rajewsky, K. (1995) Inducible gene targeting in mice. Science, 269, 1427–1429 · DOI · Paper page
  24. Lewandoski, M. (2001) Conditional control of gene expression in the mouse. Nat Rev Genet, 2, 743–755 · DOI
  25. Saam, J.R. and Gordon, J.I. (1999) Inducible gene knockouts in the small intestinal and colonic epithelium. J Biol Chem, 274, 38071–38082 · DOI
  26. St-Onge, L., Furth, P.A. and Gruss, P. (1996) Temporal control of the Cre recombinase in transgenic mice by a tetracycline responsive promoter. Nucleic Acids Res, 24, 3875–3877 · DOI
  27. Utomo, A.R., Nikitin, A.Y. and Lee, W.H. (1999) Temporal, spatial, and cell type-specific control of Cre-mediated DNA recombination in transgenic mice. Nat Biotechnol, 17, 1091–1096 · DOI
  28. Brocard, J., Feil, R., Chambon, P. and Metzger, D. (1998) A chimeric Cre recombinase inducible by synthetic, but not by natural ligands of the glucocorticoid receptor. Nucleic Acids Res, 26, 4086–4090 · DOI
  29. Feil, R., Brocard, J., Mascrez, B., LeMeur, M., Metzger, D. and Chambon, P. (1996) Ligand-activated site-specific recombination in mice. Proc Natl Acad Sci U S A, 93, 10887–10890 · DOI · Paper page
  30. Feil, R., Wagner, J., Metzger, D. and Chambon, P. (1997) Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains. Biochem Biophys Res Commun, 237, 752–757 · DOI
  31. Kellendonk, C., Tronche, F., Casanova, E., Anlag, K., Opherk, C. and Schutz, G. (1999) Inducible site-specific recombination in the brain. J Mol Biol, 285, 175–182 · DOI
  32. Kellendonk, C., Tronche, F., Monaghan, A.P., Angrand, P.O., Stewart, F. and Schutz, G. (1996) Regulation of Cre recombinase activity by the synthetic steroid RU 486. Nucleic Acids Res, 24, 1404–1411 · DOI
  33. Indra, A.K., Warot, X., Brocard, J., Bornert, J.M., Xiao, J.H., Chambon, P. and Metzger, D. (1999) Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases. Nucleic Acids Res, 27, 4324–4327 · DOI
  34. Feil, R. (2007) Conditional somatic mutagenesis in the mouse using site-specific recombinases. Handb Exp Pharmacol, 178, 3–28 · DOI
  35. Hunter, N.L., Awatramani, R.B., Farley, F.W. and Dymecki, S.M. (2005) Ligand-activated Flpe for temporally regulated gene modifications. Genesis, 41, 99–109 · DOI
  36. Collins, F.S., Rossant, J. and Wurst, W. (2007) A mouse for all reasons. Cell, 128, 9–13 · DOI
  37. Schwenk, F., Kuhn, R., Angrand, P.O., Rajewsky, K. and Stewart, A.F. (1998) Temporally and spatially regulated somatic mutagenesis in mice. Nucleic Acids Res, 26, 1427–1432 · DOI
  38. Vooijs, M., Jonkers, J. and Berns, A. (2001) A highly efficient ligand-regulated Cre recombinase mouse line shows that LoxP recombination is position dependent. EMBO Rep, 2, 292–297 · DOI
  39. Thyagarajan, B., Guimaraes, M.J., Groth, A.C. and Calos, M.P. (2000) Mammalian genomes contain active recombinase recognition sites. Gene, 244, 47–54 · DOI
  40. Forni, P.E., Scuoppo, C., Imayoshi, I., Taulli, R., Dastru, W., Sala, V., Betz, U.A., Muzzi, P., Martinuzzi, D., Vercelli, A.E. et al (2006) High levels of Cre expression in neuronal progenitors cause defects in brain development leading to microencephaly and hydrocephaly. J Neurosci, 26, 9593–9602 · DOI
  41. Loonstra, A., Vooijs, M., Beverloo, H.B., Allak, B.A., van Drunen, E., Kanaar, R., Berns, A. and Jonkers, J. (2001) Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells. Proc Natl Acad Sci U S A, 98, 9209–9214 · DOI
  42. Schmidt, E.E., Taylor, D.S., Prigge, J.R., Barnett, S. and Capecchi, M.R. (2000) Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Proc Natl Acad Sci U S A, 97, 13702–13707 · DOI
  43. Furr, B.J. and Jordan, V.C. (1984) The pharmacology and clinical uses of tamoxifen. Pharmacol Ther, 25, 127–205 · DOI
  44. Danielian, P.S., Muccino, D., Rowitch, D.H., Michael, S.K. and McMahon, A.P. (1998) Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr Biol, 8, 1323–1326 · DOI
  45. Vasioukhin, V., Degenstein, L., Wise, B. and Fuchs, E. (1999) The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin. Proc Natl Acad Sci U S A, 96, 8551–8556 · DOI
  46. Brocard, J., Warot, X., Wendling, O., Messaddeq, N., Vonesch, J.L., Chambon, P. and Metzger, D. (1997) Spatio-temporally controlled site-specific somatic mutagenesis in the mouse. Proc Natl Acad Sci U S A, 94, 14559–14563 · DOI
  47. Schuler, M., Dierich, A., Chambon, P. and Metzger, D. (2004) Efficient temporally controlled targeted somatic mutagenesis in hepatocytes of the mouse. Genesis, 39, 167–172 · DOI
  48. Mataki, C., Magnier, B.C., Houten, S.M., Annicotte, J.S., Argmann, C., Thomas, C., Overmars, H., Kulik, W., Metzger, D., Auwerx, J. et al (2007) Compromised intestinal lipid absorption in mice with a liver-specific deficiency of liver receptor homolog 1. Mol Cell Biol, 27, 8330–8339 · DOI
  49. Schnutgen, F., Doerflinger, N., Calleja, C., Wendling, O., Chambon, P. and Ghyselinck, N.B. (2003) A directional strategy for monitoring Cre-mediated recombination at the cellular level in the mouse. Nat Biotechnol, 21, 562–565 · DOI
  50. Schnutgen, F. and Ghyselinck, N.B. (2007) Adopting the good reFLEXes when generating conditional alterations in the mouse genome. Transgenic Res, 16, 405–413 · DOI
  51. Schnutgen, F., De-Zolt, S., Van Sloun, P., Hollatz, M., Floss, T., Hansen, J., Altschmied, J., Seisenberger, C., Ghyselinck, N.B., Ruiz, P. et al (2005) Genomewide production of multipurpose alleles for the functional analysis of the mouse genome. Proc Natl Acad Sci U S A, 102, 7221–7226 · DOI
  52. Wirth, D., Gama-Norton, L., Riemer, P., Sandhu, U., Schucht, R. and Hauser, H. (2007) Road to precision: recombinase-based targeting technologies for genome engineering. Curr Opin Biotechnol, 18, 411–419 · DOI
  53. Coroadinha, A.S., Schucht, R., Gama-Norton, L., Wirth, D., Hauser, H. and Carrondo, M.J. (2006) The use of recombinase mediated cassette exchange in retroviral vector producer cell lines: predictability and efficiency by transgene exchange. J Biotechnol, 124, 457–468 · DOI
  54. Schucht, R., Coroadinha, A.S., Zanta-Boussif, M.A., Verhoeyen, E., Carrondo, M.J., Hauser, H. and Wirth, D. (2006) A new generation of retroviral producer cells: predictable and stable virus production by Flp-mediated site-specific integration of retroviral vectors. Mol Ther, 14, 285–292 · DOI
  55. Toledo, F., Liu, C.W., Lee, C.J. and Wahl, G.M. (2006) RMCE-ASAP: a gene targeting method for ES and somatic cells to accelerate phenotype analyses. Nucleic Acids Res, 34, e92 · DOI
  56. Seibler, J., Kleinridders, A., Kuter-Luks, B., Niehaves, S., Bruning, J.C. and Schwenk, F. (2007) Reversible gene knockdown in mice using a tight, inducible shRNA expression system. Nucleic Acids Res, 35, e54 · DOI
  57. Seibler, J., Kuter-Luks, B., Kern, H., Streu, S., Plum, L., Mauer, J., Kuhn, R., Bruning, J.C. and Schwenk, F. (2005) Single copy shRNA configuration for ubiquitous gene knockdown in mice. Nucleic Acids Res, 33, e67 · DOI
  58. Torres, R.M. and Kühn, R. (1997) In: Torres, R.M. and Kühn, R. (eds.), Laboratory protocols for conditional gene targeting. Oxford University Press, Oxford, pp. 167 · DOI
  59. Zhang, Y., Riesterer, C., Ayrall, A.M., Sablitzky, F., Littlewood, T.D. and Reth, M. (1996) Inducible site-directed recombination in mouse embryonic stem cells. Nucleic Acids Res, 24, 543–548 · DOI
  60. Logie, C. and Stewart, A.F. (1995) Ligand-regulated site-specific recombination. Proc Natl Acad Sci U S A, 92, 5940–5944 · DOI
  61. Littlewood, T.D., Hancock, D.C., Danielian, P.S., Parker, M.G. and Evan, G.I. (1995) A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. Nucleic Acids Res, 23, 1686–1690 · DOI
  62. Weber, P., Metzger, D. and Chambon, P. Temporally controlled targeted somatic mutagenesis in the mouse brain. European Journal of Neuroscience, 14, 1777–1783 · DOI

Cited by

Sorted by citations

See all 106

Metadata

Authors
Birling, M.-C., Gofflot, F., & Warot, X.
Affiliations
Phénotypage et ingénierie précliniques des systèmes d’organismes modèles (FR)
Venue
Methods in Molecular Biology
Publisher
Humana Press
Published
2009
Volume
561
Pages
245-263
ISSN
  • 1064-3745 (ISSN-L)
  • 1940-6029
OpenAlex
W1747944491
Cited by
106
References
2
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 2 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 8 · 2013: 9 · 2012: 14
FWCI
13.46
Type
book chapter
Language
en
Open access
Licence
other-oa
Locations
  • Methods in molecular biology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • DIAL (Catholic University of Leuven) (submittedVersion)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
site-specific recombination, Cre recombinase, Flp recombinase, phiC31 integrase, conditional gene targeting, mouse model
MeSH terms
Animals, DNA Nucleotidyltransferases, Genetic Engineering, Mutagenesis, Genome, Gene Targeting, Animals, Genetically Modified, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Site-Specific Recombinases for Manipulation of the Mouse Genome. https://app.cochat.ai/papers/10.1007/978-1-60327-019-9_16
The paper
Birling, M.-C., Gofflot, F., & Warot, X. (2009). Site-Specific Recombinases for Manipulation of the Mouse Genome. Methods in Molecular Biology. https://doi.org/10.1007/978-1-60327-019-9_16