Mammalian genome targeting using site-specific recombinases

Frontiers in Bioscience

Volumn 11, Issue 1 P.889-1198, 2006, Pages 1108-1136

  García Otín, Angel Luis ^a   Guillou, Florian ^b  

^a HOSPITAL UNIVERSITARIO MIGUEL SERVET   (Spain)

^b UMR85 PHYSIOLOGIE DE LA REPRODUCTION ET DES COMPORTEMENTS   (France)

Author keywords

Conditional Gene Targeting; Genetically Modified Mouse Models; Mouse; Review; Site Specific Recombinase; Spatial And Temporal Gene Inactivation

Indexed keywords

MAMMALIA;

EID: 32844468662     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/1867     Document Type: Review

References (308)

1. Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520-562 (2002)
2. Guenet JL. Chemical mutagenesis of the mouse genome: an overview. Genetica 122: 9-24 (2004)
3. Justice MJ, JK Noveroske, JS Weber, B Zheng & A Bradley. Mouse ENU mutagenesis. Hum Mol Genetics 8: 1955-1963 (1999)
4. Zambrowicz BP & GA Friedrich. Comprehensive mammalian genetics: history and future prospects of gene trapping in the mouse. Int J Dev Biol 42: 1025-1036 (1998)
5. Lyons GE, BJ Swanson, MA Haendel & J Daniels. Gene trapping in embryonic stem cells in vitro to identify novel developmentally regulated genes in the mouse. Methods Mol Biol 136: 297-307 (2000)
6. Nagy A. Cre recombinase: the universal reagent for genome tailoring. Genesis 26: 99-109 (2000)
7. Wells T & DA Carter. Genetic engineering of neural function in transgenic rodents: towards a comprehensive strategy? J Neurosci Methods 108: 111-130 (2001)
8. Lewandoski M. Conditional control of gene expression in the mouse. Nat Rev Genet 2: 743-755 (2001)
9. Ryding ADS, MGF Sharp & JJ Mullins. Conditional transgenic technologies. J Endocrinol 171: 1-14 (2001)
10. Bockamp E, M Maringer, C Spangenberg, S Fees, S Fraser, L Eshkind, Foesch & B Zabel. Of mice and models: improved animal models for biomedical research. Physiol Genomics 11: 115-132 (2002)
11. Van der Meyden L, DJ Adams & A Bradley. Tools for targeted manipulation of the mouse genome. Physiol Genomics 11: 133-164 (2002)
12. Tronche F, E Casanova, M Turiault, I Sahly & C Kellendonk. When reverse genetics meets physiology: the use of site-specific recombinases in mice. FEBS Lett 529: 116-121 (2002)
13. Prosser H & S Rastan. Manipulation of the mouse genome: a multiple impact resource for drug discovery and development. Trends Biotechnol 21: 224-232 (2003)
14. Gao J, X Wu & J Zuo. Targeting hearing genes in mice. Mol Brain Res 132: 192-207 (2004)
15. Giuriato S, K Rabin, AC Fan, CM Shachaf & DW Felsher. Conditional animal models: a strategy to define when oncogenes will be effective targets to treat cancer. Sem Cancer Biol 14: 3-11 (2004)
16. Austin S, M Ziese & N Sternberg. A novel role for site-specific recombination in maintenance of bacterial replicons. Cell 25: 729-736 (1981)
17. Van Duyne GD. A structural view of cre-loxP site-specific recombination. Annu Rev Biophys Biomol Struct 30: 87-104 (2001)
18. Ghosh K & GD Van Duyne. Cre-loxP biochemistry. Methods 28: 374-383 (2002)
19. Volkert FC, LC Wu, PA Fisher & JR Broach. Survival strategies of the yeast plasmid two-micron circle. Basic Life Sci 40: 375-396 (1986)
20. Chen Y & PA Rice. New insight into site-specific recombination from Flp recombinase-DNA structures. Annu Rev Biophys Biomol Struct 32: 135-159 (2003)
21. Heidmann D & CF Lehner. Reduction of Cre recombinase toxicity in proliferating Drosophila cells by estrogen-dependent activity regulation. Dev Genes Evol 211: 458-465 (2001)
22. McGuire SE, G Roman & RL Davis. Gene expression systems in Drosophila: a synthesis of time and space. Trends Genet 20: 384-391 (2004)
23. Dong J & GW Stuart. Transgene manipulation in zebrafish by using recombinases. Methods Cell Biol 77: 363-379 (2004)
24. Werdien D, G Peiler & GU Ryffel. FLP and Cre recombinase function in Xenopus embryos. Nucleic Acids Res 29: e53 (2001)
25. Srivastava V & DW Ow. Marker-free site-specific gene integration in plants. Trends Biotechnol 22: 627-629 (2004)
26. Sauer B & N Henderson. Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage Pl. Proc Natl Acad Sci USA 85: 5166-5170 (1988)
27. Fukushige S & B Sauer. Genomic targeting with a positive-selection lox integration vector allows highly reproducible gene expression in mammalian cells. Proc Natl Acad Sci USA 89: 7095-7099 (1992)
28. Beaubonis W & B Sauer. Genomic targeting with purified Cre recombinase. Nucleic Acids Res 21: 2025-2029 (1993)
29. Westerman KA & P Leboulch. Reversible immortalization of mammalian cells mediated by retroviral transfer and site-specific recombination. Proc Natl Acad Sci USA 93: 8971-8976 (1996)
30. Orban PC, D Chui & JD Marth. Tissue- and site-specific DNA recombination in transgenic mice. Proc Natl Acad Sci USA 89: 6861-6865 (1992)
31. Sunaga S, K Maki, Y Komagata, K Ikuta & JI Miyazaki. Efficient removal of loxP-flanked DNA sequences in a gene-targeted locus by transient expression of Cre recombinase in fertilized eggs. Mol Reprod Dev 46: 109-113 (1997)
32. de Wit T, D Drabek & F Grosveld. Microinjection of ere recombinase RNA induces site specific-recombination of a transgene in mouse oocytes. Nucleic Acids Res 26: 676-678 (1998)
33. Schaft J, R Ashery-Padan, F van der Hoeven, P Gruss & AF Stewart. Efficient FLP recombination in mouse ES cells and oocytes. Genesis 31: 6-10 (2001)
34. Vooijs M, J Jonkers & A Berns. A highly efficient ligand-regulated Cre recombinase mouse line shows that LoxP recombination is position dependent. EMBO Rep 2: 292-297 (2001)
35. Will E, H Klump, N Heffner, M Schwieger, B Schiedlmeier, W Ostertag, C Baum & C Stocking. Unmodified Cre recombinase crosses the membrane. Nucleic Acids Res 30: e59 (2002)
36. Jo D, Q Lin, A Nashabi, DJ Mays, D Unutmaz, JA Pietenpol & HE Ruley. Cell cycle-dependent transduction of cell-permeant Cre recombinase proteins. J Cell Biochem 89: 674-687 (2003)
37. Fiering S, E Epner, K Robinson, Y Zhuang, A Telling, M Hu, DI Martin, T Enver, TJ Ley & M Groudine. Targeted deletion of 5'HS2 of the murine beta-globin LCR reveals that is not essential for proper regulation of the beta-globin locus. Genes Dev 9: 2203-2213 (1995)
38. Dymecki SM. Flp recombinase promotes site-specific DNA recombination in embryonic stem cells and transgenic mice. Proc Natl Acad Sci USA 93: 6191-6196 (1996)
39. Buchholz F, L Ringrose, PO Angrand, F Rossi & AF Stewart. Different thermostabilities of FLP and Cre recombinases: implications for applied site-specific recombination. Nucleic Acids Res 24: 4256-4262 (1996)
40. Thyagarajan B, MJ Guimaraes, AC Groth & MP Calos. Mammalian genomes contain active recombinase recognition sites. Gene (2000); 244: 47.
41. Hollis RP, SM Stall, CR Sclimenti, J Lin, Y Chen-Tsai & MP Calos. Phage integrases for the construction and manipulation of transgenic mammals. Reprod Biol Endocrinol 1: 79 (2003)
42. Heidmann D & CF Lehrer. Reduction of Cre recombinase toxicity in proliferating Drosophila cells by estrogen-dependent activity regulation. Dev Genes Evol 211: 458-465 (2001)
43. Mahonen AJ, KJ Airenne, MM Lind, HP Lesch & S Yla-Herttuala. Optimized self-excising cassette for mammalian cells. Biochem Biophys Res Commun 320: 366-371 (2004)
44. Schmidt EE, DS Taylor, JR Prigge, S Barnett & MR Cappechi. Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Proc Natl Acad Sic USA 97: 13702-13707 (2000)
45. Koresawa Y, M Miyagawa, M Ikawa, K Katsunami, M Yamada, M Okabe & R Shirakura. A new Cre recombinase based on optimal codon usage in mammals: a powerful material for organ-specific gene targeting. Transplant Proc 32: 2516-2517 (2000)
46. Shimshek DR, J Kim, MR Hubner, DJ Spergel, F Buchholz, E Casanova, AF Stewart, PH Seeburg & R Sprengel. Codon-improved Cre Recombinase (iCre) expression in the mouse. Genesis 32: 19-26 (2002)
47. Buchholz F, PO Angrand & AF Stewart. Improved properties of FLP recombinase evolved by cycling mutagenesis. Nat Biotechnol 16: 657-662 (1998)
48. Rodriguez CI, F Buchholz, J Galloway, R Seguerra, J Kasper, R Ayala, AF Stewart & SM Dymecki. High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 25: 139-140 (2000)
49. Parley FW, P Soriano, LS Steifen & SM Dymecki. Widespread recombinase expression using FLPeR (flipper) mice. Genesis 28: 106-110 (2000)
50. Andreas S, F Schwenk, B Küter-Luks, N Faust & R Kühn. 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 (2002)
51. Le Y, S Gagneten, D Tombaccini, B Behtke & B Sauer. Nuclear target determinants of the phage P1 Cre DNA recombinase. Nucleic Acids Res 27: 4703-4709 (1999)
52. Gu H, YR Zou & K Rajewsky. Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting. Cell 6: 1155-1164 (1993)
53. Peitz M, K Pfannkuche, K Rajewsky & F Edenholfer. 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: 4489-4494 (2002)
54. Jo D, A Nashabi, C Doxsee, Q Lin, D Unutmaz, J Chen & HE Ruley. Epigenetic regulation of gene stucture and function with a cell-permeable Cre recombinase. Nat Biotechnol 19: 929-933 (2001)
55. Lin Q, D jo, KD Grebre-Amlak & HE Ruley. Enhanced cell-permeant Cre protein for site-specific recombination in cultured cells. BMC Biotechnol 4:25 (2004)
56. Gagneten S, Y Le, J Miller & B Sauer. Brief expression of a GFP ere fusion gene in embryonic stem cells allows rapid retrieval of site-specific genomic deletions. Nucleic Acids Res 25: 3326-3331 (1997)
57. Striklett PK, RD Nelson & DE Kohan. Site-specific recombination using an epitope tagged bacteriophage P1 Cre recombinase. Gene 215: 415-423 (1998)
58. Picard D. Regulation of protein function through expression of chimaeric proteins. Curr Opin Biotechnol 5: 511-515 (1994)
59. Metzger D, J Clifford, H Chiba & P Chambon. Conditional site-specific recombination in mammalian cells using a ligand-dependent chimeric Cre recombinase. Proc Natl Acad Sci USA 92: 6991-6995 (1995)
60. Logie C & AF Stewart. Ligand-regulated site-specific recombination. Proc Natl Acad Sci USA 92: 5940-5944 (1995)
61. Feil R, J Brocard, B Mascrez, M LeMeur, D Metzger & P Chambon. Ligand-activated site-specific recombination in mice. Proc Natl Acad Sci USA 93: 10887-10890 (1996)
62. Feil R, J Wagner, D Metzger & P Chambon. Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains. Biochem Biophys Res Commun 237: 752-757 (1997)
63. Casanova E, S Fehsenfeld, T Lemberger, DR Shimshek, R Sprengel & T Mantamadiotis. ER-based double iCre fusion protein allows partial recombination in forebrain. Genesis 34: 208-214 (2002)
64. Zhang Y, C Riesterer, AM Ayrall, F Sablitzky, TD Littlewood & M Reth. Inducible site-directed recombination in mouse embryonic stem cells. Nucleic Acids Res 24: 543-548 (1996)
65. Brocard J, X Warot, O Wenling, N Messaddeq, JL Vonesch, P Chambon & D Metzger. Spatio-temporally controlled site-specific somatic mutagenesis in the mouse. Proc Natl Acad Sci USA 94: 14559-14563 (1997)
66. Tannour-Louet M, A Porteu, S Vaulont, A Kahn & M Vasseur-Cognet. A tamoxifen-inducible chimeric Cre recombinase specifically effective in the fetal and adult mouse liver. Hepatology 35: 1072-1081 (2002)
67. Hunter NL, RB Awatramani, FW Parley & SM Dymecki. Ligand-activated Pipe for temporally regulated gene modifications. Genesis 41: 99-109 (2005)
68. Vegeto E, GF Allan, WT Schrader, MJ Tsai, DP McDonnell & BW O'Malley. The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor. Cell 69: 703-713 (1992)
69. Kellendonk C, F Tronche, AP Monaghan, PO Angrand, F Stewart & G Schütz. Regulation of Cre recombinase activity by the synthetic steroid RU486. Nucleic Acids Res 24: 1404-1411 (1996)
70. Kellendonk C, F Tronche, E Casanova, K Anlag, C Opherk & G Schütz. Inducible site-specific recombination in the brain. J Mol Biol 285: 175-182 (1999)
71. Minamino T, V Gaussin, FJ DeMayo & MD Schneider. Inducible gene targeting in postnatal myocardium by cardiac-specific expression of a hormone-activated Cre fusion protein. Circ Res 88: 587-592 (2001)
72. Gao Y & RV Short. Fertility control in wild mice after feeding with RU486 or methyl testosterone. J Reprod Fertil 101: 483-487 (1994)
73. Youssef JA & MZ Badr. Hepatocarcinogenic potential of the glucocorticoid antagonist RU486 in B6C3F1 mice: effect on apoptosis, expression of oncogenes and the tumor suppressor gene p53. Mol Cancer 2: 3 (2003)
74. Kaczmarczyk SJ & Green JE. Induction of ere recombinase activity using modified androgen receptor ligand binding domains: a sensitive assay for ligand-receptor interactions. Nucleic Acids Res 31: e86 (2003)
75. Hoess RH, A Wierbicki & K Abremski. The role of the loxP spacer region in Pl site-specific recombination. Nucleic Acids Res 14: 2287-2300 (1986)
76. Lee G & I Saito. Role of nucleotide sequences of loxP spacer region in Cre-mediated recombination. Gene 216: 55-65 (1998)
77. Kolb AF. Selection-marker-free modification of the murine beta-casein gene using a lox2272 site. Anal Biochem 290: 260-271 (2001)
78. Albert H, EC Dale, E Lee & DW Ow. Site-specific integration of DNA into wild-type and mutant lox sites placed in the plant genome. Plant J 7: 649-659 (1995)
79. Langer SJ, AP Ghafoori, M Byrd & L Leinwand. A genetic screen identifies novel non-compatible loxP sites. Nucleic Acids Res 30: 3067-3077 (2002)
80. Buchholz F & AF Stewart. Alteration of Cre recombinase site specificity by substrate-linked protein evolution. Nat Biotecnol 19: 1047-1052 (2001)
81. Voziyanov Y, JH Konieczka, AF Stewart & M Jarayam. Stepwise manipulation of DNA specificity in FIp: progressively adapting Flp to individual and combinatorial mutations in its target site. J Mol Biol 326: 65-76 (2003)
82. Konieczka JH, A Paek M Jarayam & Y Voziyanov. Recombination of hybrid target sites by binary combinations of Flp variants: mutations that foster interpromoter collaboration and enlarge substrate tolerance. J Mol Biol 339: 365-378 (2004)
83. Casanova E, T Lemberger, S Fehsenfeld, T Mantamadiotis & G Schutz. Alpha complementation in Cre recombinase enzyme. Genesis 37: 25-29 (2003)
84. Jullien N, F Sampieri, A Enjalbert & JP Herman. Regulation of Cre recombinase by ligand-induced complementation of inactive fragments. Nucleic Acids Res 31: el31
85. Nunes-Duby SE, RS Thimmalai, HJ Kwon, T Ellenberger & A Landy. Similarities and differences among 105 members of the Int family of site-specific recombinases. Nucleic Acids Res 26: 391-406 (1998)
86. Groth AC & MP Calos. Phage integrases: biology and applications. J Mol Biol 335: 667-678 (2004)
87. Thorpe HM & MCM Smith. In vitro site-specific integration of bacteriophage DNA catalysed by a recombinase of the resolvase/invertase family. Proc Natl Acad Sci USA 95: 5505-5510 (1998)
88. Groth AC, EC Olivares, B Thyagarajan & MP Calos. A phage integrase directs efficient site-specific integration in human cells. Proc Natl Acad Sci USA 97: 5595-6000 (2000)
89. Belteki G, M Gersenstein DW Ow & A Nagy. Site-specific cassette exchange and germline transmission with mouse ES cells expressing phiC31 integrase. Nat Biotechnol 21: 321-324 (2003)
90. Thyagarajan B, EC Olivares, RP Hollis, DS Ginsburg & MC Calos. Site-specific genomic integration in mammalian cells mediated by phage phiC31 integrase. Mol Cell Biol 21: 3926-3934 (2001)
91. Sclimenti CR, B Thyagarajan & MP Calos. Directed evolution of a recombinase for improved genomic integration at a native human sequence. Nucleic Acids Res 29: 5044-5051 (2001)
92. Matsuura M, T Noguchi, D Yamaguchi, T Aida, M Asayama, H Takahashi & M Shirai. The sre gene (ORF469) encodes a site-specific recombinase responsible for integration of the R4 phage genome. J Bacteriol 178: 3374-3376 (1996)
93. Olivares EC, RP Hollis & MP Calos. Phage R4 integrase mediates site-specific integration in human cells. Gene 278: 167-76 (2001)
94. Stall SM, DS Ginsburg & MP Calos. Phage TP901-1 site specific integrase functions in human cells. J Bacteriol 184: 3657-63 (2002)
95. Christ N & P Droge. Alterations in the directionality of lambda site-specific recombinations catalysed by mutant integrases in vivo. J Mol Biol 288: 825-836 (1999)
96. Lorbach E, N Christ, M Schwikardi & P Droge. Site-specific recombination in human cells catalysed by phage lambda integrase mutants. J Mol Biol 296: 1175-1181 (2000)
97. Christ N & P Droge. Genetic manipulation of mouse embryonic stem cells by mutant lambda integrase. Genesis 32: 203-208 (2002)
98. Kolot M, N Silberstein & E Yagil. Site-specific recombination in mammalian cells expressing the Int recombinase of bacteriophage HK022. Mol Biol Rep 26: 207-213 (1999)
99. Rojo F & JC Alonso. A novel site-specific recombinase encoded by the streptomyces pyogenes plasmid pSM19035. J Mol Biol 238: 159-172 (1994)
100. Rojo F & JC Alonso. The beta recombinase of plasmid pSM19035 binds to two adjacent sites, making different contacts at each of them. Nucleic Acids Res 23: 3181-3188 (1995)
101. Alonso JC, F Weise & F Rojo. The bacillus subtilis histone-like protein Hbsu is required for DNA resolution and DNA inversion mediated by the beta recombinase of plasmid pSM19035. J Biol Chem 270: 2938-2945 (1995)
102. Diaz V, F Rojo, C Martinez-A, JC Alonso, & A Bemad. The prokaryotic beta-recombinase catalyzes site-specific recombination in mammalian cells. J Biol Chem 274: 6634-6640 (1999)
103. Alonso JC, C Gutierrez & F Rojo. The role of chromatin-associated protein Hbsu in beta-mediated recombination is to facilitate the joining of distant recombination sites. Mol Microbiol 18: 471-478 (1995)
104. Matsuzaki H, H Araki & Y Oshima. Gene conversion associated with site-specific recombination in yeast plasmid pSR1. Mol Cell Biol 2: 955-62 (1988)
105. Araki H, N Nakanishi, BR Evans, H Matsuzaki, M Jayaram & Y Oshima. Site-specific recombinase, R, encoded by yeast plasmid pSR1. J Mol Biol 225: 25-37 (1992)
106. Yang SH & M Jayaram. Generality of the shared active site among yeast family site-specific recombinases. The R site-specific recombinase follows the Flp paradigm. J Biol Chem 269: 12789-12796 (1994)
107. Onouchi H, K Yokoi, C Machida, H Matsuzaki, Y Oshima, K Matsuoka, K Nakamura & Y Machida. Operation of an efficient site-specific recombination system of Zygosaccharomyces rouxii in tobacco cells. Nucleic Acids Res 19: 6373-6378 (1991)
108. Droge P & NR Cozzarelli. Recombination of knotted substrates by Tn3 resolvase. Proc Natl Acad Sci USA 86: 6062-6066 (1989)
109. Schwikardi M & P Droge. Site-specific recombination in mammalian cells catalysed by gamma-delta resolvase mutants: implications for the topology of episomal DNA. FEBS Lett 471: 147-150 (2000)
110. Sauer B & J McDermott. DNA recombination with a heterospecific Cre homolog identified from comparison of the pac-cl regions of P1-related phages. Nucleic Acids Res 32: 6086-6095 (2004)
111. Bibb LA, MI Hancox & GF Hatfull. Integration and excision by the charge serine recombinase phiRv1 integrase. Mol Microbiol 55: 1896-1910 (2005)
112. Brinster RL, HY Chen, M Trumbauer, AW Senear, R Warren & RD Palmiter. Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Cell 27: 223-231 (1981)
113. nd ed). CSHL Press, NY (1994)
114. Dellaire G & P Chartrand. Direct evidence that transgene integration is random in murine cells, implying that naturally occurring double-strand breaks may be distributed similarly within the genome. Radiat Res 149: 325-329 (1998)
115. Miao GG, RJ Smeyne, G D'Arcangelo, NG Copeland, NA Jenkins, JI Morgan & T Curran. Isolation of an allele of reeler by insertional mutagenesis. Proc Natl Acad Sci USA 91: 11050-11054 (1994)
116. Yokoyama T, NG Copeland, NA Jenkins, CA Montgomery, FF Elder & PA Overbeek. Reversal of a left-right asymmetry: a situs inversus mutation. Science 260: 679-682 (1993)
117. Pfeifer A. Lentiviral transgenesis. Transgenic Res 13: 513-522 (2004)
118. Rülicke T & U Hübscher. Germ line transformation of mammals by pronuclear microinjection. Exp Physiol 85: 589-601 (2000)
119. Li X, W Wang & T Lufkin. Dicistronic LacZ and alkaline phosphatase reporter constructs permit simultaneous histological analysis of expression from multiple transgenes. Biotechniques 23: 874-882 (1997)
120. Antoch MP, EJ Song, AM Chang, MH Vitaterna, Y Zhao, LD Wilsbacher, AM Sangoram, DP King, LH Pinto & JS Takahashi. Functional identification of the mouse circadian clock gene by transgenic BAC rescue. Cell 89: 655-667.
121. Giraldo P & L Montoliu. Size matters: use of YACs, BACs and PACs in transgenic animals. Transgenic Res 10: 83-103 (2001)
122. Heintz N. BAC transgenesis. Nat Rev Neurosci 2: 861-870 (2001)
123. Muyrers JP, Y Zhang, G Testa & AF Stewart. Rapid modification of bacterial artificial chromosomes by ET-recombination. Nucleic Acids Res 27: 1555-1557 (1999)
124. Testa G, Y Zhang, K Vintersten, V Benes, WW Pijnappel, I Chambers, AJ Smith & AF Stewart. Engineering the mouse genome with bacterial artificial chromosomes to create multipurpose alleles. Nat Biotechnol 21: 443-447 (2003)
125. Lee EC, D Yu, JM de Velasco, L Tessarollo, DA Swing, DL Court, NA Jenkins & NG Copeland. A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA. Genomics 73: 56-65 (2001)
126. Warming S, N Costantino, DL Court, NA Jenkins & NG Copeland. Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res 33: e36 (2005)
127. Copeland NG, NA Jenkins & DL Court. Recombineering: a powerful new tool for mouse functional genomics. Nat Rev 2: 769-779 (2001)
128. Dykxhoorn DM, CD Novina & PA Sharp. Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol 4: 457-467 (2003)
129. Elbashir SM, W Lendeckel & T Tuschl. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 15: 188-200 (2001)
130. Elbashir SM, J Harborth, W Lendeckel, A Yakin, K Weber, T Tuschl. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411: 494-498 (2001)
131. Brummelkamp TR, R Bernards & R Agami. A system for stable expression of short interfering RNAs in mammalian cells. Science 296: 550-553 (2002)
132. Sui G, C Soohoo, B Affar, F Gay, Y Shi, WC Forrester & Y Shi. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc Natl Acad Sci USA 99: 5515-5520 (2002)
133. Yu JY, SL De Ruiter & DL Turner. RNA interference by expression of shirt-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci USA 99: 6047-6052 (2002)
134. Miyagishi M & K Taira. U6 promoter-driven siRNAs with four uridine 3′ overhangs efficiently suppress targeted gene expression in mammalian cells. Nat Biotechnol 20: 497-500 (2002)
135. Carmell MA, L Zhang, DS Conklin, GJ Hannon & TH Rosenquist. Germline transmission of RNAi in mice. Nat Struct Biol 10: 91-92 (2003)
136. Rubinson D, CP Dillon, AV Kwiatkowski, C Sievers, L Yang, J Kopinja, DL Rooney, MM Ihrig, MT McManus, FB Gertler, ML Scott & L Van Parijs. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet 33: 401-406 (2003)
137. Stein P, P Svoboda & RM Schulte. Transgenic RNAi in mouse oocytes: a simple and fast approach to study gene function. Dev Biol 256: 187-193 (2003)
138. McCaffrey AP, H Nakai, K Pandey, Z Huang, FH Salazar, H Xu, SF Wieland, PL Marion & MA Kay. Inhibition of hepatitis B virus in mice by RNA interference. Nat Biotechnol 21: 639-644 (2003)
139. Tiscomia G, O Singer, M Ikawa & IM Verma. A general method for gene knockdown in mice by using lentiviral vectors expressing small interfering RNA. Proc Natl Acad Sci USA 100: 1844-1848 (2003)
140. Kunath T, G Gish, H Lickert, N Jones, T Pawson & J Rossant. Transgenic RNA interference in ES cell-derived embryos recapitulates a genetic null phenotype. Nat Biotechnol 21: 559-561 (2003)
141. Thomas KR & MR Capecchi. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51: 503-512 (1987)
142. Wong EA & MR Capecchi. Analysis of homologous recombination in cultured mammalian cells in transient expression and stable transformation assays. Somat Cell Mol Genet 12: 63-72 (1986)
143. Hasty P, J Rivera-Perez & A Bradley. The length of homology required for gene targeting in embryonic stem cells. Mol Cell Biol 11: 5586-5591 (1991)
144. Lu ZH, JT Books, RM Kaufman & TJ Ley. Long targeting arms do not increase the efficiency of homologous recombination in the beta-globin locus of murine embryonic stem cells. Blood 102: 1531-1533 (2003)
145. Kumar S & JP Simons. The effects of terminal heterologies on gene targeting by insertion vectors in embryonic stem cells. Nucleic Acids Res 21: 1541-1548 (1993)
146. Hooper M, K Hardy, A Handyside, S Hunter & M Monk. HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326: 292-295 (1987)
147. Shesely EG, HS Kim, WR Sheshee, T Papayannopoulou, O Smithies & BW Popovich. Correction of a human beta S-globin gene by gene targeting. Proc Natl Acad Sci USA 88: 4294-4298 (1991)
148. Hasty P, R Ramirez-Solis, R Krumlauf & A Bradley. Introduction of a subtle mutation into the Hox-2.6 locus in embryonic stem cells. Nature 350: 243-246 (1991)
149. Askew GR, T Doetschman & J Lingrel. Site-directed point mutations in embryonic stem cells: a gene-targeting tag-and-exchange strategy. Mol Cell Biol 13: 4115-4124 (1993)
150. Whyatt LM & PD Rathjen. Introduction of precise alterations into the mouse genome with high efficiency by stable tag-exchange gene targeting: implications for gene targeting in ES cells. Nucleic Acids Res 25: 2381-2388 (1997)
151. Sakai K & J Miyazaki. A transgenic mouse line that retains Cre recombinase activity in mature oocytes irrespective of the ere transgene transmission. Biochem Biophys Res Commun 237: 318-324
152. Lallemand Y, V Luria, R Haffner-Krausz & P Lonai. Maternally expressed PGK-Cre transgene as a tool for early uniform activation of the Cre site-specific recombinase. Transgenic Res 7: 105-112 (1998)
153. Takeuchi T, Nomura T, Tsujita M, Suzuki M, Fuse T, Mori H & M Mishina. Flp recombinase transgenic mice of C57BL/6 strain for conditional gene targeting. Biochem Biophys Res Commun 293: 953-957 (2002)
154. RM Torres & R Kühn. Laboratory protocols for conditional gene targeting. Oxford University Press, NY (1997)
155. Wolfer DP, WE Cusio & HP Lipp. Knockout mices: simple solutions to the problems of genetic background and flanking genes. Trends Neurosci 25: 336-340 (2002)
156. Seong E, TL Saunders, CL Stewart & M Burmeister. To knockout in 129 or in C57BL/6: that is the question. Trends Genet 20: 59-62 (2004)
157. nd ed. (Ed. A Joyner). IRL Press. Oxford University Press (1999).
158. Li X, Y Yu, W Wei, J Yong, J Yang, X Xiong, T Qing & H Deng. Simple and efficient production of mice derived from embryonic stem cells aggregated with tetraploid embryos. Mol Reprod Dev 71: 154-158 (2005)
159. Eggan K, H Akutsu, J Loring, L Jackson-Grusby, M Klemm, WM Rideout, R Yanagimachi & R Jaenisch. Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation. Proc Natl Acad Sci USA 98: 6209-6214 (2001)
160. Misra RP, SK Bronson, Q Xiao, W Garrison, J li, R Zhao & SA Duncan. Generation of single-copy transgenic mouse embryos by tetraploid embryo complementation. BMC Biotechnol 1: 12 (2001)
161. Seibler J, B Zevnik, B Kuter-Luks, S Andreas, H Kern, T Hennek, A Rode, C Heimann, N Faust, G Kauselmann, M Schoor, R Jaenisch, K Rajewsky, R Kühn & F Schwenk. Rapid generation of inducible mouse mutants. Nucleic Acids Res 31: e12 (2003)
162. Zhou D, JX Ren, TM Ryan, NP Higgins & TM Townes. Rapid tagging of endogenous mouse genes by recombineering and ES cell complementation of tetraploid blastocysts. Nucleic Acids Res 32: e128 (2004)
163. Vintersten K, C Monetti, M Gertsenstein, P Zhang, L Laszlo, S Bichele & A Nagy. Mouse in red: red fluorescent protein expression in mouse ES cells, embryos, and adult animals. Genesis 40: 241-246 (2004)
164. Smith GR. How homologous recombination is initiated: unexpected evidence for single-strand nicks from v(d)j site-specific recombination Cell 117: 146-148 (2004)
165. Cohen-Tannoudji M, S Robine, A Choulika, D Pinto, F El Marjou, C Babinet, D Louvard & F laisser. I-Scel induced gene replacement at a natural locus in embryonic stem cells. Mol Cell Biol 18: 1444-1448 (1998)
166. Porteus MH & D Baltimore. Chimeric nucleases stimulate gene targeting in human cells. Science 300: 763 (2003)
167. Urnov FD, JC Miller, YL Lee, CM Beausejour, JM Rock, S Augustus, AC Jamieson, MH Porteus, PD Gregory & MC Holmes. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435: 646-651 (2005)
168. Wakayama T, AC Perry, M Zuccotti, KR Johnson & R Yanagimachi. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394: 369-374 (1998)
169. Wakayama T & R Yanagimachi. Cloning the laboratory mouse. Semin Cell Dev Biol 10: 253-258 (1999)
170. Yabuuchi A, Y Yasuda, Y Kato & Y Tsunoda. Effects of nuclear transfer procedures on ES cell cloning efficiency in the mouse. J Reprod Dev 50: 263-268 (2004)
171. Hiiragi T & D Solter. Reprogramming is essential in nuclear transfer. Mol Reprod Dev 70: 417-421 (2005)
172. Yanagimachi R. Cloning: experience from the mouse and other animals. Mol Cell Endocrinol 187: 241-248 (2002)
173. Jaenisch R, K Eggan, D Humphreys, W Rideout & K Hochedlinger. Nuclear cloning, stem cells, and genomic reprogramming. Cloning Stem Cells 4: 389-396 (2002)
174. Wakayama T, I Rodriguez, AC Perry, R Yanamigachi & P Mombaerts. Mice cloned from embryonic stem cells. Proc Natl Acad Sci USA 96: 14984-14989 (1999)
175. Gao S, M McGarry, H Priddle, T Ferner, B Gasparini, J Fletcher, L Harkness, P De Sousa, J McWhir & I Wilmut. Effects of donor oocytes and culture conditions on development of cloned mice embryos. Mol Reprod Dev 66: 126-133 (2003)
176. Li ZW, G Stark, J Götz, T Rülicke, U Müller & C Weissmann. Generation of mice with a 200-kb amyloid precursor protein gene deletion by Cre recombinase-mediated site-specific recombination in embryonic stem cells. Proc Natl Acad Sci USA 93: 6158-6162 (1996)
177. Zheng B, M Sage, EA Sheppeard, V Jurecic & A Bradley. Engineering mouse chromosomes with Cre-1oxP: ange, efficiency, and somatic implications. Mol Cell Biol 20: 648-655 (2000)
178. Gu H, JD Marth, PC Orban, H Mossmann & K Rajewsky. Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science 265: 103-106 (1994)
179. Holzenberger M, C Lenzner, P Leneuve, R Zaoui, G Hamard, S Vaulont & Y Le Bouc. Cre-mediated germline mosaicism: a method allowing rapid generation of several alleles of a target gene. Nucleic Acids Res 28: e92 (2000)
180. Leneuve P, S Colnot, G Hamard, F Francis, M Niwa-Kawakita, M Giovannini & M Holzenberger. Cre-mediated germline mosaicism: a new transgenic mouse for the selective removal of residual markers from tri-lox conditional alleles. Nucleic Acids Res 31: e21 (2003)
181. Sun X, M Lewandoski, EN Meyers, YH Liu, RE Maxson & GR Martin. Conditional inactivation of Fgf4 reveals complexity of signalling during limb bud development. Nat Genet 25: 83-86 (2000)
182. Schmitgen F, N Doerflinger, C Calleja, O Wendling, P Chambon & NB Ghyselinck. A directional strategy for monitoring Cre-mediated recombination at the cellular level in the mouse. Nat Biotechnol 21: 562-565 (2003)
183. Casanova E, S Fehsenfeld, T Mantamadiotis, T Lemberger, E Greiner, AF Stewart & G Schutz. A CamKIIalpha iCre BAC allows brain-specific gene inactivation. Genesis 31: 37-42 (2001)
184. Aller MI, A Jones, D Merlo, M Paterlini, AH Meyer, M Farrant & W Wisden. Cerebellar granule cell Cre recombinase expression. Genesis 36: 97-103 (2003)
185. Ohyama T & AK Groves. Generation of Pax2-Cre mice by modification of a Pax2 bacterial artificial chromosome. Genesis 38: 195-199 (2004)
186. Zhang XM, AH Ng, JA Tanner, WT Wu, NG Copeland, NA Jenkins & JD Huang. Highly restricted expression of Cre recombinase in cerebellar Purkinje cells. Genesis 40: 45-51 (2004)
187. Guo H, S Hong, XL Jin, RS Chen, PP Avasthi, YT Tu, TL Ivanco & Y Li. Specificity and efficiency of Cre-mediated recombination in Emx1-Cre knock-in mice. Biochem Biophys Res Commun 273: 661-665 (2000)
188. Voiculescu O, P Charnay & S Schneider-Maunoury. Expression pattern of a Krox-20/Cre knock-in allele in the developing hindbrain, bones, and peripheral nervous system. Genesis 26: 123-126 (2000)
189. Moses KA, F DeMayo, RM Braun, JL Reecy & RJ Schwartz. Embryonic expression of an Nkx2-5/Cre gene using ROSA26 reporter mice. Genesis 31: 176-180 (2001)
190. Motoike T, DW Markham DW, J Rossant & TN Sato. Evidence for novel fate of Flk1+ progenitor: contribution to muscle lineage. Genesis 35: 153-159 (2003)
191. Jeyasuria P, Y Ikeda, SP Jamin, L Zhao, DG De Rooij, AP Themmen, RR Behringer & KL Parker. Cell specific knockout of steroidogenic factor 1 reveals its essential roles in gonadal function. Mol Endocrinol 18: 1610-1619 (2004)
192. Zhuang X, J Masson, JA Gingrich, S Rayport & R Hen. Targeted gene expression in dopamine and serotonin neurons of the mouse brain. J Neurosci Methods 143: 27-32 (2005)
193. Kiwura J, Y Suda, D Kurosawa, ZM Hossain, M Nakawura, M Takahashi, A Mara & S Aizawa. Emx2 and Pax6 function in cooperation with Otx2 and Otx1 to develop caudal forebrain primordium that includes future archipalium. J Neurosci 25: 5097-5108 (2005)
194. Lappe-Siefke C, S Goebbels, M Gravel, E Nicksch, J Lee, PE Braun, IR Griffiths & KA Nave. Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination. Nat Genet 33: 366-374 (2003)
195. Saito H, H Tsumura, S Otake, A Nishida, T Furukawa & N Suzuki. L7/Pcp-2-specific expression of Cre recombinase using knock-in approach. Biochem Biophys Res Commun 331: 1216-1221 (2005)
196. Gorski JA & KR Jones. Efficient bicistronic expresion of ere in mammalian cells. Nucleic Acids Res 27: 2059-2061 (1999)
197. Stanley EG, C Biben, A Elefanty, L Bamett, F Koentgen, L Robb & RP Harvey. Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3′UTR-ires-Cre allele of the homeobox gene Nkx2-5. Int J Dev Biol 46: 431-439 (2002)
198. Vincent SD & EJ Robertson Targeted insertion of an 1RES Cre into the Hnf4alpha locus: Cre-mediated recombination in the liver, kidney, and gut epithelium. Genesis 39: 206-211 (2004)
199. Michael SK, J Brennan & EJ Robertson. Efficient gene-specific expression of Cre recombinase in the mouse embryo by targeted insertion of a novel IRES-Cre cassette into endogenous loci. Mech Dev 85: 35-47 (1999)
200. Mallo M. Controlled gene activation and inactivation in the mouse. Front Biosci 11: 313-327 (2006)
201. Zhu Z, T Zeng, CG lee, RJ Homer & JA Elias. Tetracycline-controlled transcriptional regulation systems: advances and application in transgenic animal modelling. Semin Cell Dev Biol 13: 121-128 (2002)
202. Sawicki JA, B Monks & RJ Morris. Cell-specific ecdysone-inducible expression of FLP recombinase in mammalian cells. Biotechniques 25: 868-875 (1998)
203. Utomo ARH, AY Nikitin & WH Lee. Temporal, spatial, and cell type-specific control of Cre-mediated DNA recombination in transgenic mice. Nat Biotechnol 17: 1091-1096 (1999)
204. Linderberg J, R Mattsson & T Ebendal. Timing of doxycycline yields different patterns of genomic recombination in brain neurons with a new inducible Cre transgene. J Neurosci Res 68: 248-253 (2002)
205. Saam JR & JI Gordon. Inducible gene knockouts in the small intestine and colonic epithelium. J Biol Chem 274: 38071-38082 (1999)
206. Schönig K, F Schwenk, K Rajewsky & H Bujard. Stringent doxycycline dependent control of CRE recombinase in vivo. Nucleic Acids Res 30: e134 (2002)
207. Perl AK, SE Wert, A Nagy, CG Lobe, JA Whittsett. Early restriction of peripheral and proximal cell lineages during formation of the lung. Proc Natl Acad Sci USA 99: 10482-10487 (2002)
208. Schuler M, F Ali, E Metzger, P Chambon & D Metzger. Temporally controlled targeted somatic mutagenesis in skeletal muscles of the mouse. Genesis 41: 165-170 (2005)
209. Kim JE, K Nakashima & B de Crombrugghe. Transgenic mice expressing a ligand-inducible ere recombinase in osteoblasts and odontoblasts: a new tool to examine physiology and disease of postnatal bone and tooth. Am J Pathol 165: 1875-1882 (2004)
210. Metzger D, M Li & P Chambon. Targeted somatic mutagenesis in the mouse epidermis. Methods Mol Biol 289: 329-340 (2005)
211. Schuler M, A Dierich, P Chambon & D Metzger. Efficient temporally controlled targeted somatic mutagenesis in hepatocytes of the mouse. Genesis 39: 167-172 (2004)
212. Zhu HZ, JQ Chen, GX Cheng & JL Xue. Generation and characterization of transgenic mice expressing tamoxifen-inducible cre-fusion protein specifically in mouse liver. World J Gastroenterol 9: 1844-1847 (2003)
213. Leone DP, S Genoud, S Atanasoski, R Grausenburger, P Berger, D Metzger, WB Macklin, P Chambon & U Suter. Tamoxifen-inducible glia-specific Cre mice for somatic mutagenesis in oligodendrocytes and Schwann cells. Mol Cell Neurosci 22: 430-440 (2003)
214. Doerflinger NH, WB Macklin & B Popko. Inducible site-specific recombination in myelinating cells. Genesis 35: 63-72 (2003)
215. Bugeon L, A Danou, D Carpentier, P Langridge, N Syed & MJ Dallman. Inducible gene silencing in podocytes: a new tool for studying glomerular fonction. J Am Soc Nephrol 14: 786-791 (2003)
216. Weber P, M Schuler, C Gerard, M Mark, D Metzger & P Chambon. Temporally controlled site-specific mutagenesis in the germ cell lineage of the mouse testis. Biol Reprod 68: 553-559 (2003)
217. Forde A, R Constien, HJ Grone, G Hammerling & B Arnold. Temporal Cre-mediated recombination exclusively in endothelial cells using Tie2 regulatory elements. Genesis 33: 191-197 (2002)
218. Zheng B, Z Zhang, CM Black, B de Crombrugghe & CP Denton. Ligand-dependent genetic recombination in fibroblasts: a potentially powerful technique for investigating gene function in fibrosis. Am J Pathol 160: 1609-1617 (2002)
219. el Marjou F, KP Janssen, BH Chang, M Li, V Hindie, L Chan, D Louvard, P Chambon, D Metzger & S Robine. Tissue-specific and inducible Cre-mediated recombination in the gut epithelium. Genesis 39: 186-193 (2004)
220. Wen F, G Cecena, V Munoz-Ritchie, E Fuchs, P Chambon & RG Oshima. Expression of conditional ere recombinase in epithelial tissues of transgenic mice. Genesis 35: 100-106 (2003)
221. Bex A, M Vooijs, S Horenblas & A Berns. Controlling gene expression in the urothelium using transgenic mice with inducible bladder specific Cre-lox recombination. J Urol 168: 2641-2644 (2002)
222. Kemp R, H Ireland, E Clayton, C Houghton, L Howard & DJ Winton. Elimination of background recombination: somatic induction of Cre by combined transcriptional regulation and hormone binding affinity. Nucleic Acids Res 32: e92 (2004)
223. Brake RL, PJ Simmons & CG Begley. Cross-contamination with tamoxifen induces transgene expression in non-exposed inducible transgenic mice. Genet Mol Res 3: 456-462 (2004)
224. Boutonnet C, O Boijoux, S Bernat, A Kharrat, G Fabre, JC Faye & S Vagner. Pharmacological-based translational induction of transgene expression in mammalian cells. EMBO Rep 5: 721-727 (2004)
225. Sakai M, K Mitani & J Miyazaki. Efficient regulation of gene expression by adenovirus vector mediated delivery of CRE recombinase. Biochem Biophys Res Commun 217: 393-401 (1995)
226. Kanegae Y, K Takamori, Y Sato, G Lee, M Nakai & I Saito. Efficient gene activation system on mammalian cell chromosomes using recombinant adenovirus producing Cre recombinase. Gene 181: 207-212 (1996)
227. Nakano M, K Odaka, M Ishimura, S Kondo, N Tachikawa, J Chiba, Y Kanegae & I Saito. Efficient gene activation in cultured mammalian cells mediated by FLP recombinase-expressing recombinant adenovirus. Nucleic Acids Res 29: e40 (2001)
228. Shui JW & TH Tan. Germline transmission and efficient DNA recombination in mouse embryonic stem cells mediated by adenoviral-Cre transduction. Genesis 39: 217-223 (2004)
229. Stec DE, RL Davidson, RE Haskell, BL Davidson & CD Sigmund. Efficient liver-specific deletion of a floxed human angiotensinogen transgene by adenoviral delivery of Cre recombinase in vivo. J Biol Chem 274: 21285-21290 (1999)
230. Thevenot E, F Cote, P Colin, Y He, H Leblois, M Perricaudet, J Mallet & G Vodjdani. Targeting conditional gene modification into the serotonin neurons of the dorsal raphe nucleus by viral delivery of Cre recombinase. Mol Cell Neurosci 24: 139-147 (2003)
231. Kaspar BK, B Vissel, T Bengoechea, S Crone, L Randolph-Moore, R Muller, EP Brandon, D Schaffer, IM Verma, KF Lee, SF Heinemann & FH Gage. Adeno-associated virus effectively mediates conditional gene modification in the brain. Proc Natl Acad Sci USA 99: 2320-2325 (2002)
232. Sinnayah P, TE Lindley, PD Staber, BL Davidson, MD Cassell & RL Davidson. Targeted viral delivery of Cre recombinase induces conditional gene deletion in cardiovascular circuits of the mouse brain. Physiol Genomics 18: 25-32 (2004)
233. Meuwissen R, SC Linn, M van der Valk, WJ Mooi & A Berns. Mouse model for lung tumorigenesis through Cre/lox controlled sporadic activation of the K-Ras oncogene. Oncogene 20: 6551-6558 (2001)
234. Siprashvili Z & PA Khavari. Lentivectors for regulated and reversible cutaneous gene delivery. Mol Ther 9: 93-100 (2004)
235. Iwatate M, Y Gu, T Dieterle, Y Iwanaga, KL Peterson, M Hoshijima, KR Chien & J Ross. In vivo high-efficiency transcoronary gene delivery and Cre-loxP gene switching in the adult mouse heart. Gene Ther 10: 1814-1820 (2003)
236. Leow CC, XD Wang & WQ Gao. Novel method of generating prostate-specific Cre-LoxP gene switching via intraductal delivery of adenovirus. Prostate 65: 1-9 (2005)
237. Pfeifer A, EP Brandon, N Koostra, FH Gage & IM Verma. Delivery of Cre recombinase by a self-deleting lentiviral vector: efficient gene targeting in vivo. Proc Natl Acad Sci USA 98: 11450-11455 (2001)
238. Silver DP & DM Livingston. Self-exciding retroviral vectors encoding Cre recombinase overcome Cre-mediated cellular toxicity. Mol Cell 8: 233-243 (2001)
239. Rinaldi A, KR Marshall & CM Preston. A non-cytotoxic herpes simpex virus vector which expresses Cre recombinase directs efficient site specific recombination. Virus Res 65: 11-20 (1999)
240. Leblois H, C Roche, N Di Falco, C Orsini, P Yeh & M Perricaudet. Stable transduction of actively dividing cells via a novel adenoviral/episomal vector. Mol Ther 1: 314-322 (2000)
241. Oehmig A, C Fraefel, XO Breakefield & M Ackermann. Herpes simplex virus type 1 amplicons and their hybrid virus partners, EBV, AAV, and retrovirus. Curr Gene Ther 4: 385-408 (2004)
242. Kasim V, M Miyagashi & K Taira. Control of siRNA expression using the Cre-loxP recombination system. Nucleic Acids Res 32: e66 (2004)
243. Fritsch L, LA Martinez, R Sekhri, I Naguibneva, M Gérard, M Vandromme, L Schaeffer & A Harel Bellan. Conditional gene knock-down by CRE-dependent short interfering RNAs. EMBO Rep 5: 178-182 (2004)
244. Tiscornia G, V Tergaonkar F Galimi & IM Verma. CRE recombinase-inducible RNA interference mediated by lentiviral vectors. Proc Natl Acad Sci USA 101: 7347-7351 (2004)
245. Coumoul X, W Li, RH Wang & C Deng. Inducible suppression of Fgfr2 and Survivin in ES cells using a combination of the RNA interference (RNAi) and the Cre-LoxP system. Nucleic Acids Res 32: e85 (2004)
246. Ventura A, A Meissner, CP Dillon, M McManus, PA Sharp, L Van Parijs, R Jaenisch & T Jacks. Cre-lox regulated RNA interference from transgenes. Proc Natl Acad Sci USA 101: 10380-10385 (2004)
247. Mallo M, B Kanzler & S Ohnemus. Reversible gene inactivation in the mouse. Genomics 81: 356-360 (2003)
248. Lakso M, B Sauer, B Mosinger, EJ Lee, RW Manning, SH Yu, KL Mulder & H Westphal. Targeted oncogene activation by site-specific recombination in transgenic mice. Proc Natl Acad Sci USA 89: 6232-6236 (1992)
249. Poliri K, M Szabolcs, P Fisher, A Kljuijc, T Ludwig & A Efstratiadis. A mouse model of uterine leiomyosarcoma. Am J Pathol 164: 325-336 (2004)
250. Belteki G, Haigh J, N Kabacs, K Haigh, K Sison, F Costantini, J Whitsett, SE Quaggin & A Nagy. Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction. Nucleic Acids Res 33: e51 (2005)
251. Lieu HD, SK Withycombe, Q Walker, JX Rong, RL Walzern, JS Wong, RL Hamilton, EA Fisher & SG Young. Eliminating atherogenesis in mice by switching off hepatic lipoprotein secretion. Circulation 107: 1315-1321 (2003)
252. McLean GW, NH Komiyama, B Serrels, H Asano, L Reynolds, F Conti, K Hodivala-Dilke, D Metzger, P Chambon, SG Grant & MC Frame. Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression. Genes Dev 18: 2998-3003 (2005)
253. Gothert JR, SE Gustin, JA van Eekelen, U Schmidt, MA Hall, SM Jane, AR Green, B Gottgens, DJ Izon & CG Begley. Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium. Blood 104: 1769-1777 (2004)
254. Imai T, R Takakuwa, S Marchand, E Dentz, JM Bornert, N Messaddeq, O Wendung, M Mark, B Desvergne, W Wahli, P Chambon & D Metzger. Peroxisome proliferator-activated receptor gamma is required in mature white and brown adipocytes for their survival in the mouse. Proc Natl Acad Sci USA 101: 4543-4547 (2004)
255. Kostetskii I, J Li, Y Xiong, R Zhou, VA Ferrari, W Patel, JD Molkentin & GL Radice. Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure. Circ Res 96: 346-354 (2005)
256. Eckardt D, M Theis, J Degen, T Ott, HV van Rijen, S Kirchhoff, JS Kim, JM de Bakker & K Willecke. Functional role of connexin43 gap junction channels in adult mouse heart assessed by inducible gene deletion. J Mol Cell Cardiol 36: 101-110 (2004)
257. Kroll J, P Cobo & TN Sato. Versatile inducible activation system of Akt/PKB signalling pathway in mice. Genesis 35: 160-163 (2003)
258. Petrich BG, JD Molkentin & Y Wang. Temporal activation of c-Jun N-terminal kinase in adult transgenic heart via cre-loxP-mediated DNA recombination. FASEB J 17: 749-751 (2003)
259. McMinn JE, SM Liu, I Dragatsis, P Dietrich, T Ludwig, S Eiden & SC Chua. An allelic series for the leptin receptor gene generated by CRE and FLP recombinase. Mamm Genome 15: 677-685 (2004)
260. Smith AJ, MA Oe Sousa, B Kwabi-Addo, A Heppell-Parton, P Impey & P Rabbits. A site-directed chromosomal translocation induced in embryonic stem cells by Cre-loxP recombination. Nat Genet 9: 376-385 (1995)
261. Van Deursen J, M Fornerod, B Van Rees & G Grosveld. Cre-mediated site-specific translocation between nonhomologous mouse chromosomes. Proc Natl Acad Sci USA 92: 7376-7380 (1995)
262. Yu Y & A Bradley. Engineering chromosomal rearrangements in mice. Nat Rev Genet 2: 780-790 (2001)
263. Lindsay EA, A Botta, V Jurecic, S Carattini-Rivera, YC Cheah, HM Rosenblatt, A Bradley & A Baldini. Congenital heart disease in mice deficient for the DiGeorge syndrome region. Nature 401: 379-383 (1999)
264. Lewandoski M & GR Martin. Cre-mediated chromosome loss in mice. Nat Genet 17: 223-225 (1997)
265. Herault Y, M Rassoultzadegan, F Cuzin & D Duboule. Engineering chromosomes in mice through targeted meiotic recombination (TAMERE) Nature 20: 381-384 (1998)
266. Buchholz F, Y Rafaeli, A Trumpp & JM Bishop. Inducible chromosomal translocation of AML1 and ETO genes through Cre/loxP-mediated recombination in the mouse. EMBO Rep 1: 133-139 (2000)
267. Forster A, R Pannell, LF Drynan M McCormack EC Collins, A Daser & TH Rabbits. Engineering de novo reciprocal chromosomal translocations associated with M11 to replicate primary events of human cancer. Cancer Cell 3: 449-458 (2003)
268. Collins EC, R Pannel, EM Simpson, A Forster & TH Rabbits. Inter-chromosomal recombination of M11 and Af9 genes mediated by cre-loxP in mouse development. EMBO Rep 1: 127-132 (2000)
269. Zheng B, AA Mills & A Bradley. A system for rapid generation of coat color-tagged knockouts and defined chromosomal rearrangements in mice. Nucleic Acids Res 27: 2354-2360 (1999)
270. Adams DJ, PJ Biggs, T Cox, R Davies, L van der Weyden, J Jonkers, J Smith, B Plumb, R Taylor, I Nishijima, Y Yu, J Rogers & A Bradley. Mutagenic Insetion and Chromosome Engineering Resource (MICER). Nat Genet 36: 867-871 (2004)
271. Koike H, K Horie, H Fukuyama, G Kondoh, S Nagata & J Takeda.Efficient biallelic mutagenesis with Cre/loxP-mediated interchromosomal recombination. EMBO Rep 3: 433-437 (2002)
272. Minasi LE, Y Kamogawa, S Carding, K Bottomly & RA Flavell. The selective ablation of interleukin 2-producing cells isolated from transgenic mice. J Exp Med 177: 1451-1459 (1993)
273. Delaney CL, M Brenner & A Messing. Conditional ablation of cerebellar astrocytes in postnatal transgenic mice. J Neurosci 16: 6908-6918 (1996)
274. Mathis C, C Hindelang, M LeMeur & E Borrelli. A transgenic mouse model for inducible and reversible dysmyelination. J Neurosci 20: 7698-7705 (2000)
275. Garcia AD, NB Doan, T Imura, TG Bush & MV Sofroniew. GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat Neurosci 7: 1233-1241 (2004)
276. Grieshammer U, M Lewandoski, D Prevette, RW Oppenheim & GR Martin. Muscle-specific cell ablation conditional upon Cre-mediated DNA recombination in transgenic mice leads to massive spinal and cranial motoneuron loss. Dev Biol 197: 234-247 (1998)
277. Herrera PL, L Orci & JD Vassalli. Two transgenic approaches to define the cell lineages in endocrine pancreas development. Mol Cel Endocrinol 140, 45-50 (1998)
278. Brockschnieder D, C Lappe-Siefke, S Goebbels, MR Boesl, KA Nave & D Riethmacher. Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination. Mol Cell Biol 24: 7636-7642 (2004)
279. Buch T, FL Heppner, C Tertilt, TJ Keinen, M Kremer, FT Wunderlich, S Jung & A Waisman. A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration. Nat Methods 2: 419-426 (2005)
280. Chen YT, R Levasseur, S Vaishnav, G Karsenty & A Bradley. Bigenic Cre/loxP, puDeltatk conditional genetic ablation. Nucleic Acids Res 32: e61 (2004)
281. Sato M, Y Yasuoka, H Kodama, T Watanabe, JI Miyazaki & M Kimura. New approach to cell lineage analysis in mammals using the Cre-loxP system. Mol Reprod Dev 56: 34-44 (2000)
282. Araki K, M Araki, J Miyazaki & P Vassalli. Site-specific recombination of a transgene in fertilized eggs by transient expression of Cre recombinase. Proc Natl Acad Sci USA 92: 160-164 (1995)
283. St-Onge L, PA Furth & P Grass. Temporal control of Cre recombinase in transgenic mice by a tetracycline responsive promoter. Nucleic Acids Res 24: 3875-3877 (1996)
284. Akagi K, V Sandig, M Vooijs, M Van der Valk, M Giovannini, M Strauss & A Berns. Cre-mediated somatic site-specific recombination in mice. Nucleic Acids Res 25: 1766-1773 (1997)
285. Thorey IS, Muth K, Russ AP, J Otte, A Reffelmann & H von Melchner. Selective disruption of genes transiently induced in differentiating mouse embryonic stem cells by using gene trap mutagenesis and site-specific recombination. Mol Cell Biol 18: 3081-3088 (1998)
286. Soriano P. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21: 70-71 (1999)
287. Mao X, Y Fujiwara & SH Orkin. Improved reporter strain for monitoring Cre recombinase-mediated DNA excisions in mice. Proc Natl Acad Sci USA 96: 5037-5042 (1999)
288. Kawamoto S, H Niwa, F Tashiro, S Sano, G Kondoh, J Takeda, K Tabayashi & J Miyazaki. A novel reporter mouse strain that expresses enhanced green fluorescent protein upon Cre-mediated recombination. FEBS Lett 470: 263-268 (2000)
289. Mao X, Y Fujiwara, A Chapdelaine, H Yang & SH Orkin. Activation of EGFP expression by Cre-mediated excision in a new ROSA26 reporter mouse strain. Blood 97: 324-326 (2001)
290. Srinivas S, T Watanabe, CS Lin, CM William, Y Tanabe, TM Jessell & F Costantini. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol 1: 4 (2001)
291. Safran M, WY Kim, AL Kung, JW Horner, RA De Pinho & WG Kaelin. Mouse reporter strain for non-invasive bioluminescent imaging of cells that have undergone Cre-mediated recombination. Mol Imaging 2: 297-302 (2003)
292. Novak A, C Quo, W Yang, A Nagy & CG Lobe. Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision. Genesis 28: 147-155 (2000)
293. Awatramani R, P Soriano, JJ Mai & S Dymecki. An FLP indicator mouse expressing alkaline phosphatase from the ROSA26 locus. Nat Genet 29: 257-259 (2001)
294. Zong H, JS Espinosa, HH Su, MD Muzumbar & L Luo. Mosaic analysis with double markers in mice. Cell 121: 479-492 (2005)
295. Bonaventure P, L Umans, MHM Bakker, P Cras, X Langlois, WHML Luyten, AAHP Megens, L Serneels, F van Leuven & JE Leysen. Humanization of mouse 5-hydroxytryptamine IB receptor gene by homologous recombination. Mol Pharm 56: 54-67 (1999)
296. Zou YR, W Muller H Gu & K Rajewsky. Cre-loxP-mediated gene replacement: a mouse strain producing humanized antibodies. Curr Biol 4: 1099-1103 (1994)
297. Nebert DW, TP Dalton, GW Stuart & MJ Carvan. "Gene-swap knock-in" cassette in mice to study allelic differences in human genes. Ann NY Acad Sci 919: 148-170 (2000)
298. Schake T & J Bode. Use of mutated FLP-recognition-target (FRT) sites for the exchange of expression cassettes at defined chromosomal loci. Biochemistry 33: 12746-12751 (1994)
299. Seibler J, D Schubeler, S Fiering, M Groudine & J Bode. DNA cassette exchange in ES cells mediated by Flp recombinase: an efficient strategy for repeated modification of tagged loci by marker free-constructs. Biochemistry 37: 6229-6234 (1998)
300. Soukharev S, JL Miller & B Sauer. Segmental genomic replacement in embryonic stem cells by double lox targeting. Nucleic Acids Res 27: e21 (1999)
301. Araki K, M Araki & K Yamamura. Site-directed integration of the ere gene mediated by Cre recombinase using a combination of mutant lox sites. Nucleic Acids Res 30: e103 (2002)
302. Feng YQ, J Seibler, R Alami, A Eisen, KA Westerman, P Leboulch, S Fiering & EE Bouhassira. Site-specific chromosomal integration in mammalian cells: highly efficient CRE recombinase-mediated cassette exchange. J Mol Biol 292: 779-785
303. Baer A & J Bode. Coping with kinetic and thermodynamic barriers: RMCE, an efficient strategy for the targeted integration of transgenes. Curr Opin Biotechnol 12: 473-480 (2001)
304. Lauth M, F Spreafico, K Dethleffsen & M Meyer. Stable and efficient cassette exchange under non-selectable conditions by combined use of two site-specific recombinases. Nucleic Acids Res 30: e115 (2002)
305. Lauth M, K Moerl, JJ Barski & M Meyer. Characterization of Cre-mediated cassette exchange after plasmid microinjection in fertilized mouse oocytes. Genesis 27: 153-158 (2000)
306. Cobellis G, G Nicolaus, M Iovino, A Romito, E Marra, M Barbarisi, M Sardiello, FP Di Giorgio, N Iovino, M Zollo, A Ballabio & R Cortesse. Tagging genes with cassette-exchange sites. Nucleic Acids Res 33: e44 (2005)
307. Olivares EC, RP Hollis, TW Chalberg, L Meuse, MA Kay & MP Calos. Site-specific genomic integration produces therapeutic Factor IX levels in mice. Nat Biotechnol 20: 1124-1128 (2002)
308. Schnütgen F, S De-Zolt, P Van Sloun, M Hollatz, T Floss, J Hansen, J Altschmied, C Seisenberger, Norbert B. Ghyselinck, Patricia Ruiz, Pierre Chambon, W Wurst & H von Melchner. Genomewide production of multipurpose alleles for the functional analysis of the mouse genome. Proc Natl Acad Sci USA 102: 7221-7226 (2005)