Skip to main content
SpringerLink
Log in

Cre/loxP, Flp/FRT Systems and Pluripotent Stem Cell Lines

  • Chapter
  • First Online:
Book cover Site-directed insertion of transgenes

Part of the book series: Topics in Current Genetics ((TCG,volume 23))

Abstract

Cre and FLP recombinases are the most widely used site-specific recombinases in genome engineering. Both are members of the tyrosine class of recombinases and catalyze the reversible, site-specific recombination between two identical sequences of 34 bp length in the absence of accessory factors. The substrate sequences for Cre and Flp recombinases are called loxP and FRT sites respectively. Cre recombinase was discovered in the E. coli bacteriophage P1 where it plays a crucial role in the life cycle of P1 while Flp recombinase was originally derived from the 2 μ circle of Saccharomyces cerevisiae and catalyzes recombination between inverted repeats within the 2 μ plasmid. This chapter shall provide a brief historical perspective on the discovery and early development of the Cre/loxP and FRT/FLP systems citing key studies that paved the way for the application of these site-specific recombination technologies to the engineering of mammalian genomes. Also included are discussions on the mechanisms of Cre/loxP and FRT/FLP systems application of these site-specific recombinase technologies to the introduction of transgenes in human pluripotent stem cells. Certain studies using mouse pluripotent stem cells will also be discussed in order to highlight the possibility of adopting the same strategy in their human counterparts. Lastly, future prospects for these two site-specific recombinases will be presented.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abremski K, Hoess R, Sternberg N (1983) Studies on the properties of P1 site-specific recombination: evidence for topologically unlinked products following recombination. Cell 32(4):1301–1311, PubMed PMID: 6220808

    Article  CAS  Google Scholar 

  • Albert H, Dale EC, Lee E, Ow DW (1995) Site-specific integration of DNA into wild-type and mutant lox sites placed in the plant genome. Plant J 7(4):649–659, PubMed PMID: 7742860

    Article  CAS  Google Scholar 

  • Anastassiadis K, Fu J, Patsch C, Hu S, Weidlich S, Duerschke K, Buchholz F, Edenhofer F, Stewart AF (2009) Dre recombinase, like Cre, is a highly efficient site-specific recombinase in E. coli, mammalian cells and mice. Dis Model Mech 2(9–10):508–515, Epub 2009 Aug 19. PubMed PMID: 19692579

    Article  CAS  Google Scholar 

  • Andrews BJ, Proteau GA, Beatty LG, Sadowski PD (1985) The FLP recombinase of the 2 micron circle DNA of yeast: interaction with its target sequences. Cell 40(4):795–803, PubMed PMID: 3879971

    Article  CAS  Google Scholar 

  • Araki K, Okada Y, Araki M, Yamamura K (2010) Comparative analysis of right element mutant lox sites on recombination efficiency in embryonic stem cells. BMC Biotechnol 10:29, PubMed PMID: 20356367; PubMed Central PMCID: PMC2865440

    Article  Google Scholar 

  • Austin S, Ziese M, Sternberg N (1981) A novel role for site-specific recombination in maintenance of bacterial replicons. Cell 25(3):729–736, PubMed PMID: 7026049

    Article  CAS  Google Scholar 

  • BACPAC Resources website http://bacpac.chori.org

  • Baer A, Bode J (2001) Coping with kinetic and thermodynamic barriers: RMCE, an efficient strategy for the targeted integration of transgenes. Curr Opin Biotechnol 12(5):473–480, Review. PubMed PMID: 11604323

    Article  CAS  Google Scholar 

  • Beggs JD (1978) Transformation of yeast by a replicating hybrid plasmid. Nature 275(5676):104–109, PubMed PMID: 357984

    Article  CAS  Google Scholar 

  • Bode J, Schlake T, Iber M, Schübeler D, Seibler J, Snezhkov E, Nikolaev L (2000) The transgeneticist’s toolbox: novel methods for the targeted modification of eukaryotic genomes. Biol Chem 381(9–10):801–813, Review. PubMed PMID: 11076013

    CAS  Google Scholar 

  • Broach JR, Hicks JB (1980) Replication and recombination functions associated with the yeast plasmid, 2 mu circle. Cell 21(2):501–508, PubMed PMID: 7407923

    Article  CAS  Google Scholar 

  • Broach JR, Guarascio VR, Jayaram M (1982) Recombination within the yeast plasmid 2mu circle is site-specific. Cell 29(1):227–234, PubMed PMID: 6286142

    Article  CAS  Google Scholar 

  • Brons IG, Smithers LE, Trotter MW, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes SM, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA, Vallier L (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448(7150):191–195, Epub 2007 Jun 27. PubMed PMID: 17597762

    Article  CAS  Google Scholar 

  • Buchholz F, Angrand PO, Stewart AF (1998) Improved properties of FLP recombinase evolved by cycling mutagenesis. Nat Biotechnol 16(7):657–662, PubMed PMID: 9661200

    Article  CAS  Google Scholar 

  • Buecker C, Chen HH, Polo JM, Daheron L, Bu L, Barakat TS, Okwieka P, Porter A, Gribnau J, Hochedlinger K, Geijsen N (2010) A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells. Cell Stem Cell 6(6):535–546, PubMed PMID: 20569691

    Article  CAS  Google Scholar 

  • Chen Y, Narendra U, Iype LE, Cox MM, Rice PA (2000) Crystal structure of a Flp recombinase-Holliday junction complex: assembly of an active oligomer by helix swapping. Mol Cell 6(4):885–897, PubMed PMID: 11090626

    CAS  Google Scholar 

  • Costa M, Dottori M, Ng E, Hawes SM, Sourris K, Jamshidi P, Pera MF, Elefanty AG, Stanley EG (2005) The hESC line Envy expresses high levels of GFP in all differentiated progeny. Nat Methods 2(4):259–260, Epub 2005 Mar 23. PubMed PMID: 15782217

    Article  CAS  Google Scholar 

  • Dang DT, Perrimon N (1992) Use of a yeast site-specific recombinase to generate embryonic mosaics in Drosophila. Dev Genet 13(5):367–375

    Article  CAS  Google Scholar 

  • Di Domenico AI, Christodoulou I, Pells SC, McWhir J, Thomson AJ (2008) Sequential genetic modification of the hprt locus in human ESCs combining gene targeting and recombinase-mediated cassette exchange. Cloning Stem Cells 10(2):217–230, PubMed PMID: 18386992

    Article  Google Scholar 

  • Du ZW, Hu BY, Ayala M, Sauer B, Zhang SC (2009) Cre recombination-mediated cassette exchange for building versatile transgenic human embryonic stem cells lines. Stem Cells 27(5):1032–1041, PubMed PMID: 19415769; PubMed Central PMCID: PMC2801346

    Article  CAS  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292(5819):154–156, PubMed PMID: 7242681

    Article  CAS  Google Scholar 

  • Fiering S, Kim CG, Epner EM, Groudine M (1993) An “in-out” strategy using gene targeting and FLP recombinase for the functional dissection of complex DNA regulatory elements: analysis of the beta-globin locus control region. Proc Natl Acad Sci USA 90(18):8469–8473, PubMed PMID: 8378321; PubMed Central PMCID: PMC47378

    Article  CAS  Google Scholar 

  • Fiering S, Epner E, Robinson K, Zhuang Y, Telling A, Hu M, Martin DI, Enver T, Ley TJ, Groudine M (1995) Targeted deletion of 5′HS2 of the murine beta-globin LCR reveals that it is not essential for proper regulation of the beta-globin locus. Genes Dev 9(18):2203–2213, PubMed PMID: 7557375

    Article  CAS  Google Scholar 

  • Ghosh K, Lau CK, Gupta K, van Duyne GD, Ghosh K, Lau CK, Gupta K, van Duyne GD (2005) Preferential synapsis of loxP sites drives ordered strand exchange in Cre-loxP site-specific recombination. Nat Chem Biol 1(5):275–282, Epub 2005 Sep 11. PubMed PMID: 16408057

    Article  CAS  Google Scholar 

  • Gossen M, Bujard H (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 89(12):5547–5551, PubMed PMID: 1319065; PubMed Central PMCID: PMC49329

    Article  CAS  Google Scholar 

  • Grindley ND, Whiteson KL, Rice PA, Grindley ND, Whiteson KL, Rice PA (2006) Mechanisms of site-specific recombination. Annu Rev Biochem 75:567–605, Review. PubMed PMID: 16756503

    Article  CAS  Google Scholar 

  • Gu H, Zou YR, Rajewsky K (1993) Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting. Cell 73(6):1155–1164, PubMed PMID: 8513499

    Article  CAS  Google Scholar 

  • Guhr A, Kurtz A, Friedgen K, Löser P (2006) Current state of human embryonic stem cell research: an overview of cell lines and their use in experimental work. Stem Cells 24(10):2187–2191, Epub 2006 Jun 15. Review. PubMed PMID: 16778154

    Article  Google Scholar 

  • Gump JM, Dowdy SF (2007) TAT transduction: the molecular mechanism and therapeutic prospects. Trends Mol Med 13(10):443–448, Review. PubMed PMID: 17913584

    Article  CAS  Google Scholar 

  • Guo F, Gopaul DN, van Duyne GD (1997) Structure of Cre recombinase complexed with DNA in a site-specific recombination synapse. Nature 389(6646):40–46, PubMed PMID: 9288963

    Article  CAS  Google Scholar 

  • Hochman L, Segev N, Sternberg N, Cohen G (1983) Site-specific recombinational circularization of bacteriophage P1 DNA. Virology 131(1):11–17, PubMed PMID: 6228057

    Article  CAS  Google Scholar 

  • Hoess RH, Abremski K (1985) Mechanism of strand cleavage and exchange in the Cre-lox site-specific recombination system. J Mol Biol 181(3):351–362, PubMed PMID: 3856690

    Article  CAS  Google Scholar 

  • Hoess RH, Ziese M, Sternberg N (1982) P1 site-specific recombination: nucleotide sequence of the recombining sites. Proc Natl Acad Sci USA 79(11):3398–3402, PubMed PMID: 6954485; PubMed Central PMCID: PMC346427

    Article  CAS  Google Scholar 

  • Hoess R, Wierzbicki A, Abremski K (1985) Formation of small circular DNA molecules via an in vitro site-specific recombination system. Gene 40(2–3):325–329

    Article  CAS  Google Scholar 

  • Hoess RH, Wierzbicki A, Abremski K (1986) The role of the loxP spacer region in P1 site-specific recombination. Nucleic Acids Res 14(5):2287–2300, PubMed PMID: 3457367; PubMed Central PMCID: PMC339658

    Article  CAS  Google Scholar 

  • Invitrogen website http://www.invitrogen.com

  • Irion S, Luche H, Gadue P, Fehling HJ, Kennedy M, Keller G (2007) Identification and targeting of the ROSA26 locus in human embryonic stem cells. Nat Biotechnol 25(12):1477–1482, Epub 2007 Nov 25. PubMed PMID: 18037879

    Article  CAS  Google Scholar 

  • Lee G, Saito I (1998) Role of nucleotide sequences of loxP spacer region in Cre-mediated recombination. Gene 216(1):55–65, PubMed PMID: 9714735

    Article  CAS  Google Scholar 

  • Littlewood TD, Hancock DC, Danielian PS, Parker MG, Evan GI, Littlewood TD, Hancock DC, Danielian PS, Parker MG, Evan GI (1995) A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. Nucleic Acids Res 23(10):1686–1690, PubMed PMID: 7784172; PubMed Central PMCID: PMC306922

    Article  CAS  Google Scholar 

  • Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78(12):7634–7638, PubMed PMID: 6950406; PubMed Central PMCID: PMC349323

    Article  CAS  Google Scholar 

  • McLeod M, Craft S, Broach JR (1986) Identification of the crossover site during FLP-mediated recombination in the Saccharomyces cerevisiae plasmid 2 microns circle. Mol Cell Biol 6(10):3357–3367, PubMed PMID: 3540590; PubMed Central PMCID: PMC367081

    CAS  Google Scholar 

  • Nakatsuji N, Suemori H (2002) Embryonic stem cell lines of nonhuman primates. ScientificWorldJournal 2:1762–1773, Review. PubMed PMID: 12806169

    Article  Google Scholar 

  • Nolden L, Edenhofer F, Haupt S, Koch P, Wunderlich FT, Siemen H, Brüstle O (2006) Site-specific recombination in human embryonic stem cells induced by cell-permeant Cre recombinase. Nat Methods 3(6):461–467, PubMed PMID: 16721380

    Article  CAS  Google Scholar 

  • Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448(7151):313–317, Epub 2007 Jun 6. PubMed PMID: 17554338

    Article  CAS  Google Scholar 

  • Patsch C, Peitz M, Otte DM, Kesseler D, Jungverdorben J, Wunderlich FT, Brüstle O, Zimmer A, Edenhofer F (2010) Engineering cell-permeant FLP recombinase for tightly controlled inducible and reversible overexpression in embryonic stem cells. Stem Cells 28(5):894–902, PubMed PMID: 20333748

    CAS  Google Scholar 

  • Peitz M, Pfannkuche K, Rajewsky K, Edenhofer F (2002) Ability of the hydrophobic FGF and basic TAT peptides to promote cellular uptake of recombinant Cre recombinase: a tool for efficient genetic engineering of mammalian genomes. Proc Natl Acad Sci USA 99(7):4489–4494, Epub 2002 Mar 19. PubMed PMID: 11904364; PubMed Central PMCID: PMC123675

    Article  CAS  Google Scholar 

  • Placantonakis DG, Tomishima MJ, Lafaille F, Desbordes SC, Jia F, Socci ND, Viale A, Lee H, Harrison N, Tabar V, Studer L (2009) BAC transgenesis in human embryonic stem cells as a novel tool to define the human neural lineage. Stem Cells 27(3):521–532, PubMed PMID: 19074416

    Article  CAS  Google Scholar 

  • Rank GH, Arndt GM, Xiao W (1989) FLP-FRT mediated intrachromosomal recombination on a tandemly duplicated YEp integrant at the ILV2 locus of chromosome XIII in Saccharomyces cerevisiae. Curr Genet 15(2):107–112, PubMed PMID:2663188

    Article  CAS  Google Scholar 

  • Raymond CS, Soriano P (2007) High-efficiency FLP and PhiC31 site-specific recombination in mammalian cells. PLoS One 2(1):e162, PubMed PMID: 17225864; PubMed Central PMCID: PMC1764711

    Article  Google Scholar 

  • Ringrose L, Lounnas V, Ehrlich L, Buchholz F, Wade R, Stewart AF (1998) Comparative kinetic analysis of FLP and cre recombinases: mathematical models for DNA binding and recombination. J Mol Biol 284(2):363–384, PubMed PMID: 9813124

    Article  CAS  Google Scholar 

  • Sakurai K, Shimoji M, Tahimic CG, Aiba K, Kawase E, Hasegawa K, Amagai Y, Suemori H, Nakatsuji N (2010) Efficient integration of transgenes into a defined locus in human embryonic stem cells. Nucleic Acids Res 38(7):e96, Epub 2010 Jan 13. PubMed PMID: 20071742; PubMed Central PMCID: PMC2853137

    Article  Google Scholar 

  • Sauer B (1987) Functional expression of the cre-lox site-specific recombination system in the yeast Saccharomyces cerevisiae. Mol Cell Biol 7(6):2087–2096, PubMed PMID: 3037344; PubMed Central PMCID: PMC365329

    CAS  Google Scholar 

  • Sauer B, Henderson N (1988) Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci USA 85(14):5166–5170, PubMed PMID: 2839833; PubMed Central PMCID: PMC281709

    Article  CAS  Google Scholar 

  • Schlake T, Bode J (1994) Use of mutated FLP recognition target (FRT) sites for the exchange of expression cassettes at defined chromosomal loci. Biochemistry 33(43):12746–12751, PubMed PMID: 7947678

    Article  CAS  Google Scholar 

  • Schmidt EE, Taylor DS, Prigge JR, Barnett S, Capecchi MR (2000) Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Proc Natl Acad Sci USA 97(25):13702–13707, PubMed PMID: 11087830; PubMed Central PMCID: PMC17639

    Article  CAS  Google Scholar 

  • Segev N, Cohen G (1981) Control of circularization of bacteriophage P1 DNA in Escherichia coli. Virology 114(2):333–342, PubMed PMID: 7027600

    Article  CAS  Google Scholar 

  • Senecoff JF, Cox MM (1986) Directionality in FLP protein-promoted site-specific recombination is mediated by DNA-DNA pairing. J Biol Chem 261(16):7380–7386, PubMed PMID: 3711092

    CAS  Google Scholar 

  • Shimshek DR, Kim J, Hübner MR, Spergel DJ, Buchholz F, Casanova E, Stewart AF, Seeburg PH, Sprengel R (2002) Codon-improved Cre recombinase (iCre) expression in the mouse. Genesis 32(1):19–26, PubMed PMID: 11835670

    Article  CAS  Google Scholar 

  • Siegel RW, Jain R, Bradbury A (2001) Using an in vivo phagemid system to identify non-compatible loxP sequences. FEBS Lett 499(1–2):147–153, Corrected and republished in: FEBS Lett. 2001 Sep 21;505(3):467–73. PubMed PMID: 11418130

    Article  CAS  Google Scholar 

  • Soriano P (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21(1):70–71, PubMed PMID: 9916792

    Article  CAS  Google Scholar 

  • Soukharev S, Miller JL, Sauer B (1999) Segmental genomic replacement in embryonic stem cells by double lox targeting. Nucleic Acids Res 27(18):e21, PubMed PMID: 10471751; PubMed Central PMCID: PMC148613

    Article  CAS  Google Scholar 

  • Sternberg N, Hamilton D (1981) Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites. J Mol Biol 150(4):467–486, PubMed PMID: 6276557

    Article  CAS  Google Scholar 

  • Sternberg N, Hamilton D, Hoess R (1981) Bacteriophage P1 site-specific recombination. II. Recombination between loxP and the bacterial chromosome. J Mol Biol 150(4):487–507, PubMed PMID: 6276558

    Article  CAS  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676, Epub 2006 Aug 10. PubMed PMID: 16904174

    Article  CAS  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872, PubMed PMID: 18035408

    Article  CAS  Google Scholar 

  • Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP, Mack DL, Gardner RL, McKay RD (2007) New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448(7150):196–199, Epub 2007 Jun 27. PubMed PMID: 17597760

    Article  CAS  Google Scholar 

  • Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, Becker RA, Hearn JP (1995) Isolation of a primate embryonic stem cell line. Proc Natl Acad Sci USA 92(17):7844–7848, PubMed PMID: 7544005; PubMed Central PMCID: PMC41242

    Article  CAS  Google Scholar 

  • Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, Hearn JP (1996) Pluripotent cell lines derived from common marmoset (Callithrix jacchus) blastocysts. Biol Reprod 55(2):254–259, PubMed PMID: 8828827

    Article  CAS  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147, Erratum in: Science 1998 Dec 4;282(5395):1827. PubMed PMID: 9804556

    Article  CAS  Google Scholar 

  • Thyagarajan B, Guimarães MJ, Groth AC, Calos MP (2000) Mammalian genomes contain active recombinase recognition sites. Gene 244(1–2):47–54, PubMed PMID: 10689186

    Article  CAS  Google Scholar 

  • Vetter D, Andrews BJ, Roberts-Beatty L, Sadowski PD (1983) Site-specific recombination of yeast 2-micron DNA in vitro. Proc Natl Acad Sci USA 80(23):7284–7288, PubMed PMID: 6316354; PubMed Central PMCID: PMC390039

    Article  CAS  Google Scholar 

  • Wu S, Ying G, Wu Q, Capecchi MR (2007) Toward simpler and faster genome-wide mutagenesis in mice. Nat Genet 39(7):922–930, Epub 2007 Jun 17. PubMed PMID: 17572674

    Article  CAS  Google Scholar 

  • Zambrowicz BP, Imamoto A, Fiering S, Herzenberg LA, Kerr WG, Soriano P (1997) Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc Natl Acad Sci USA 94(8):3789–3794, PubMed PMID: 9108056; PubMed Central PMCID: PMC20519

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Endocrine Research Unit, San Francisco Veterans Affairs Medical Center, Building 6 Room 312, 4150 Clement St., 94121, San Francisco, California, USA

    Candice G. T. Tahimic

  2. Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Kenji Sakurai & Norio Nakatsuji

  3. Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Ushinomiyacho, Sakyo-ku, Kyoto, 606-8501, Japan

    Kazuhiro Aiba & Norio Nakatsuji

Authors
  1. Candice G. T. Tahimic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenji Sakurai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuhiro Aiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Norio Nakatsuji
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kazuhiro Aiba or Norio Nakatsuji .

Editor information

Editors and Affiliations

  1. , UFR des Sciences Pharmaceutiques, Université François Rabelais, Parc Grandmont, Tours, 37200, France

    Sylvaine Renault

  2. Cellectis SA, Rue de la Croix Jarry 8, Paris, 75013, France

    Philippe Duchateau

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Tahimic, C.G.T., Sakurai, K., Aiba, K., Nakatsuji, N. (2013). Cre/loxP, Flp/FRT Systems and Pluripotent Stem Cell Lines. In: Renault, S., Duchateau, P. (eds) Site-directed insertion of transgenes. Topics in Current Genetics, vol 23. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4531-5_7

Download citation

Publish with us

Policies and ethics

Search

Navigation