中国农业科学 ›› 2011, Vol. 44 ›› Issue (15): 3252-3263.doi: 10.3864/j.issn.0578-1752.2011.15.021
赵爱春, 龙定沛, 谭兵, 许龙霞, 向仲怀
收稿日期:
2010-09-28
修回日期:
2010-11-21
出版日期:
2011-08-01
发布日期:
2010-12-08
通讯作者:
赵爱春,Tel:023-68250793,Fax:023-68251128,E-mail:zhaoaichun@hotmail.com;zhaoaichun@swu.edu.cn
作者简介:
赵爱春,Tel:023-68250793,Fax:023-68251128,E-mail:zhaoaichun@hotmail.com;zhaoaichun@swu.edu.cn
基金资助:
中国博士后科学基金项目(20070420722,200801221)、国家大学生创新性实验计划项目(081063503)、高等学校学科创新引智计划 (B07045)、重庆市自然科学基金计划重点项目(CSTC,2011BA1005)
ZHAO Ai-Chun, LONG Ding-Pei, TAN Bing, XU Long-Xia, XIANG Zhong-Huai
Received:
2010-09-28
Revised:
2010-11-21
Online:
2011-08-01
Published:
2010-12-08
Contact:
Ai-Chun ZHAO
摘要: 来源于酵母2 μm质粒的FLP/FRT位点特异性重组系统已经被广泛应用于拟南芥、水稻、小鼠、果蝇、线虫等高等真核模式生物,正逐渐成为转基因动植物研究领域进行基因操作的强有力工具。笔者综述了FLP/FRT系统的重组原理及其在高等真核生物中的应用,系统地概述了该系统在转基因植物、哺乳动物、昆虫以及其它相关高等真核模式生物中的研究现状,讨论了FLP/FRT系统在研究中存在的主要问题、应用前景和发展方向。
赵爱春, 龙定沛, 谭兵, 许龙霞, 向仲怀. FLP/FRT位点特异性重组系统在高等真核生物中的研究进展[J]. 中国农业科学, 2011, 44(15): 3252-3263.
ZHAO Ai-Chun, LONG Ding-Pei, TAN Bing, XU Long-Xia, XIANG Zhong-Huai. Progress in Research of FLP/FRT Site-Specific Recombination System in Higher Eukaryotes[J]. Scientia Agricultura Sinica, 2011, 44(15): 3252-3263.
[1]谷 欣, 黎 燕. 位点特异性重组技术研究进展. 生物技术通讯, 2005, 16(4): 417-419.Gu X, Li Y. The development of site-specific recombination. Letters in Biotechnology, 2005, 16(4): 417-419. (in Chinese)[2]滕 艳, 杨 晓. 基因打靶技术: 开启遗传学新纪元. 遗传, 2007, 29(11): 1291-1298.Teng Y, Yang X. Gene targeting: the beginning of a new era in genetics. Hereditas, 2007, 29(11): 1291-1298. (in Chinese)[3]Hartley J L, Donelson J E. Nucleotide sequence of the yeast plasmid. Nature, 1980, 286(5776): 860-865.[4]Falco S C, Li Y, Broach J R, Botstein D. Genetic properties of chromosomally integrated 2 μ plasmid DNA in yeast. Cell, 1982, 29(2): 573-584.[5]Jayaram M, Li Y Y, Broach J R. The yeast plasmid 2 μ circle encodes components required for its high copy propagation. Cell, 1983, 34(1): 95-104.[6]Volkert F C, Broach J R. Site-specific recombination promotes plasmid amplification in yeast. Cell, 1986, 46(4): 541-550.[7]Broach J R, Hicks J B. Replication and recombination functions associated with the yeast plasmid, 2 μ circle. Cell, 1980, 21(2): 501-508.[8]Volkert F C, Wilson D W, Broach J R. Deoxyribonucleic acid plasmids in yeasts. Microbiological Reviews, 1989, 53(3): 299-317.[9]Andrews B J, Proteau G A, Beatty L G, Sadowski P D. The FLP recombinase of the 2 μ circle DNA of yeast: interaction with its target sequences. Cell, 1985, 40(4): 795-803.[10]Argos P, Landy A, Abremski K, Egan J B, Haggard-Ljungquist E, Hoess R H, Kahn M L, Kalionis B, Narayana S V L, Pierson III L S, Sternberg N, Leong J M. The integrase family of site-specific recombinases: regional similarities and global diversity. The EMBO Journal, 1986, 5(2): 433-440.[11]Abremski K E, Hoess R H. Evidence for a second conserved arginine residue in the integrase family of recombination proteins. Protein Engineering, 1992, 5(1): 87-91.[12]Pan G, Luetke K, Sadowski P D. Mechanism of cleavage and ligation by FLP recombinase: classification of mutations in FLP protein by in vitro complementation analysis. Molecular and Cellular Biology, 1993, 13(6): 3167-3175.[13]Zhu X D, Sadowski P D. Cleavage-dependent ligation by the FLP recombinase. Characterization of a mutant FLP protein with an alteration in a catalytic amino acid. The Journal of Biological Chemistry, 1995, 270(39): 23044-23054.[14]Parsons R L, Evans B R, Zheng L, Jayaram M. Functional analysis of Arg-308 mutants of Flp recombinase. The Journal of Biological Chemistry, 1990, 265(8): 4527-4533.[15]Senecoff J F, Bruckner R C, Cox M M. The FLP recombinase of the yeast 2-μm plasmid: characterization of its recombination site. Proceedings of the National Academy of Sciences of the United States of America, 1985, 82(21): 7270-7274.[16]Sadowski P D. The Flp double cross system a simple efficient procedure for cloning DNA fragments. BMC Biotechnology, 2003, 3: 9.[17]Kilby N J, Snaith M R, Murray J A H. Site-specific recombinases: tools for genome engineering. Trends in Genetics, 1993, 9(12): 413-421.[18]Senecoff J F, Rossmeissl P J, Cox M M. DNA recognition by the FLP recombinase of the yeast 2 μ plasmid. A mutational analysis of the FLP binding site. Journal of Molecular Biology, 1988, 201(2): 405-421. [19]Schlake T, Bode J. Use of mutated FLP recognition target (FRT) sites for the exchange of expression cassettes at defined chromosomal loci. Biochemistry, 1994, 33(43): 12746-12751.[20]Seibler J, Schübeler D, Fiering S, Groudine M, Bode J. DNA cassette exchange in ES cells mediated by FLP recombinase: an efficient strategy for repeated modification of tagged loci by marker-free constructs. Biochemistry, 1998, 37(18): 6229-6234.[21]Cobellis G, Nicolaus G, Iovino M, Romito A, Marra E, Barbarisi M, Sardiello M, Di Giorgio F P, Iovino N, Zollo M, Ballabio A, Cortese R. Tagging genes with cassette-exchange sites. Nucleic Acids Research, 2005, 33(4): e44.[22]Cesari F, Rennekampff V, Vintersten K, Vuong L G, Seibler J, Bode J, Wiebel F F, Nordheim A. Elk-1 knock-out mice engineered by Flp recombinase-mediated cassette exchange. Genesis, 2004, 38(2): 87-92.[23]Hauser H, Spitzer D, Verhoeyen E, Unsinger J, Wirth D. New approaches towards ex vivo and in vivo gene therapy. Cells Tissues Organs, 2000, 167(2/3): 75-80.[24]Sadowski P D. The Flp recombinase of the 2-μm plasmid of Saccharomyces cerevisiae. Progress in Nucleic Acid Research and Molecular Biology, 1995, 51: 53-91.[25]Lee J, Whang I, Jayaram M. Assembly and orientation of Flp recombinase active sites on two-, three- and four-armed DNA substrates: implications for a recombination mechanism. Journal of Molecular Biology, 1996, 257(3): 532-549.[26]Lee J, Jayaram M, Grainge I. Wild-type Flp recombinase cleaves DNA in trans. The EMBO Journal, 1999, 18(3): 784-791.[27]Jayaram M. The cis-trans paradox of integrase. Science, 1997, 276(5309): 49-51.[28]Jayaram M, Crain K L, Parsons R L, Harshey R M. Holliday junctions in FLP recombination: resolution by step-arrest mutants of FLP protein. Proceedings of the National Academy of Sciences of the United States of America, 1988, 85(21): 7902-7906.[29]Chen Y, Narendra U, Iype L E, Cox M M, Rice P A. Crystal structure of a Flp recombinase-holliday junction complex: assembly of an active oligomer by helix swapping. Molecular Cell, 2000, 6(4): 885-897.[30]Sauer B. Site-specific recombination: developments and applications. Current Opinion in Biotechnology, 1994, 5(5): 521-527.[31]Branda C S, Dymecki S M. Talking about a revolution: the impact of site-specific recombinases on genetic analyses in mice. Developmental Cell, 2004, 6(1): 7-28.[32]Ow D W. 2004 SIVB congress symposium proceeding: transgene management via multiple site-specific recombination systems. In Vitro Cellular and Developmental Biology-Plant, 2005, 41(3): 213-219.[33]Lyznik L A, Mitchell J C, Hirayama L, Hodges T K. Activity of yeast FLP recombinase in maize and rice protoplasts. Nucleic Acids Research, 1993, 21(4): 969-975.[34]Sonti R V, Tissier A F, Wong D, Viret J F, Signer E R. Activity of the yeast FLP recombinase in Arabidopsis. Plant Molecular Biology, 1995, 28(6): 1127-1132.[35]Hu Q, Kononowicz-Hodges H, Nelson-Vasilchik K, Viola D, Zeng P, Liu H, Kausch A P, Chandlee J M, Hodges T K, Luo H. FLP recombinase-mediated site-specific recombination in rice. Plant Biotechnology Journal, 2008, 6(45): 176-188.[36]Li B, Li N, Duan X, Wei A, Yang A, Zhang J. Generation of marker-free transgenic maize with improved salt tolerance using the FLP/FRT recombination system. Journal of Biotechnology, 2010, 145(2): 206-213.[37]Kilby N J, Davies G J, Snaith M R, Murray J A H. FLP recombinase in transgenic plants: constitutive activity in stably transformed tobacco and generation of marked cell clones in Arabidopsis. The Plant Journal, 1995, 8(5): 637-652.[38]Luo K, Sun M, Deng W, Xu S. Excision of selectable marker gene from transgenic tobacco using the GM-gene-deletor system regulated by a heat-inducible promoter. Biotechnology Letters, 2008, 30(7): 1295-1302.[39]Woo H J, Cho H S, Lim S H, Shin K S, Lee S M, Lee K J, Kim D H, Cho Y G. Auto-excision of selectable marker genes from transgenic tobacco via a stress inducible FLP/FRT site-specific recombination system. Transgenic Research, 2009, 18(3): 455-465.[40]O'Gorman S, Fox D T, Wahl G M. Recombinase-mediated gene activation and site-specific integration in mammalian cells. Science, 1991, 251(4999): 1351-1355.[41]Dymecki S M. Flp recombinase promotes site-specific DNA recombinationin in embryonic stem cells and transgenic mice. Proceedings of the National Academy of Sciences of the United States of America, 1996, 93(12): 6191-6196.[42]Lo W H, Hwang S M, Chuang C K, Chen C Y, Hu Y C. Development of a hybrid baculoviral vector for sustained transgene expression. Molecular Therapy, 2009, 17(4): 658-666.[43]Buchholz F, Ringrose L, Angrand P O, Rossi F, Stewart A F. Different thermostabilities of FLP and Cre recombinases: implications for applied site-specific recombination. Nucleic Acids Research, 1996, 24(21): 4256-4262.[44]Buchholz F, Angrand P O, Stewart A F. Improved properties of FLP recombinase evolved by cycling mutagenesis. Nature Biotechnology, 1998, 16(7): 657-662.[45]Raymond C S, Soriano P. High-efficiency FLP and ФC31 site-specific recombination in mammalian cells. PLoS One, 2007, 2(1): e162.[46]Kondo S, Takata Y, Nakano M, Saito I, Kanegae Y. Activities of various FLP recombinases expressed by adenovirus vectors in mammalian cells. Journal of Molecular Biology, 2009, 390(2): 221-230.[47]Wu Y, Wang C, Sun H, LeRoith D, Yakar S. High-efficient FLPo deleter mice in C57BL/6J background. PLoS One, 2009, 4(11): e8054.[48]Wiberg F C, Rasmussen S K, Frandsen T P, Rasmussen L K, Tengbjerg K, Coljee V W, Sharon J, Yang C Y, Bregenholt S, Nielsen L S, Haurum J S, Tolstrup A B. Production of target-specific recombinant human polyclonal antibodies in mammalian cells. Biotechnology and Bioengineering, 2006, 94(2): 396-405.[49]Turakainen H, Saarimäki-Vire J, Sinjushina N, Partanen J, Savilahti H. Transposition-based method for the rapid generation of gene-targeting vectors to produce Cre/Flp-modifiable conditional knock-out mice. PLoS One, 2009, 4(2): e4341.[50]Golic K G, Lindquist S. The FLP recombinase of yeast catalyzes site-specific recombination in the Drosophila genome. Cell, 1989, 59(3): 499-509.[51]Morris A C, Schaub T L, James A A. FLP-mediated recombination in the vector mosquito, Aedes aegypti. Nucleic Acids Research, 1991, 19(21): 5895-5900.[52]Tomita S, Kanda T, Imanishi S, Tamura T. Yeast FLP recombinase-mediated excision in cultured cells and embryos of the silkworm, Bombyx mori (Lepidoptera: Bombycidae). Applied Entomology and Zoology, 1999, 34(3): 371-377.[53]Theodosiou N A, Xu T. Use of FLP/FRT system to study Drosophila development. Methods in Enzymology, 1998, 14(4): 355-365.[54]Golic K G, Golic M M. Engineering the Drosophila genome: chromosome rearrangements by design. Genetics, 1996, 144(4): 1693-1711.[55]Rong Y S, Golic K G. Gene targeting by homologous recombination in Drosophila. Science, 2000, 288(5473): 2013-2018.[56]Parks A L, Cook K R, Belvin M, Dompe N A, Fawcett R, Huppert K, Tan L R, Winter C G, Bogart K P, Deal J E, Deal-Herr M E, Grant D, Marcinko M, Miyazaki W Y, Robertson S, Shaw K J, Tabios M, Vysotskaia V, Zhao L, Andrade R S, Edgar K A, Howie E, Killpack K, Milash B, Norton A, Thao D, Whittaker K, Winner M A, Friedman L, Margolis J, Singer M A, Kopczynski C, Curtis D, Kaufman T C, Plowman G D, Duyk G, Francis-Lang H L. Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nature Genetics, 2004, 36(3): 288-292.[57]Siegal M L, Hartl D L. Transgene coplacement and high efficiency site-specific recombination with the Cre/loxP system in Drosophila. Genetics, 1996, 144(2): 715-726.[58]Siegal M L, Hartl D L. Application of Cre/loxP in Drosophila. Site-specific recombination and transgene coplacement. Methods in Molecular Biology, 2000, 136: 487-495.[59]Bode J, Schlake T, Iber M, Schübeler D, Seibler J, Snezhkov E, Nikolaev L. The transgeneticist's toolbox: novel methods for the targeted modification of eukaryotic genomes. Biological Chemistry, 2000, 381(9/10): 801-813.[60]Baer A, Bode J. Coping with kinetic and thermodynamic barriers: RMCE, an efficient strategy for the targeted integration of transgenes. Current Opinion in Biotechnology, 2001, 12(5): 473-480.[61]Horn C, Handler A M. Site-specific genomic targeting in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 2005, 102(35): 12483-12488.[62]Taillebourg E, Dura J M. A novel mechanism for P element homing in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 1999, 96(12): 6856-6861.[63]Lee T, Luo L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron, 1999, 22(3): 451-461.[64]Lee T, Luo L. Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development. Trends in Neurosciences, 2001, 24(5): 251-254.[65]Luo L. Fly MARCM and mouse MADM: genetic methods of labeling and manipulating single neurons. Brain Research Reviews, 2007, 55(2): 220-227.[66]Davis M W, Morton J J, Carroll D, Jorgensen E M. Gene activation using FLP recombinase in C. elegans. PLoS Genetics, 2008, 4(3): e1000028.[67]Voutev R, Hubbard E J A. A “FLP-out” system for controlled gene expression in Caenorhabditis elegans. Genetics, 2008, 180(1): 103-119.[68]Vázquez-Manrique R P, Legg J C, Olofsson B, Ly S, Baylis H A. Improved gene targeting in C. elegans using counter-selection and Flp-mediated marker excision. Genomics, 2010, 95(1): 37-46.[69]Werdien D, Peiler G, Ryffel G U. FLP and Cre recombinase function in Xenopus embryos. Nucleic Acids Research, 2001, 29(11): e53.[70]Ryffel G U, Werdien D, Turan G, Gerhards A, Gooβes S, Senkel S. Tagging muscle cell lineages in development and tail regeneration using Cre recombinase in transgenic Xenopus. Nucleic Acids Research, 2003, 31(8): e44.[71]Wong A C, Draper B W, Van Eenennaam A L. FLPe functions in zebrafish embryos. Transgenic Research, 2010: DOI 10.1007/ s11248-010-9410-9.[72]易厚富, 王金发. 异源位点特异性重组系统在植物中的研究. 遗传, 1999, 21(5): 62-66. Yi H F, Wang J F. Studies on heterogenetic site-specific recombination systems in plant. Hereditas, 1999, 21(5): 62-66. (in Chinese)[73]Halpin C. Gene stacking in transgenic plants-the challenge for 21st century plant biotechnology. Plant Biotechnology Journal, 2005, 3(2): 141-155.[74]Tomita M, Munetsuna H, Sato T, Adachi T, Hino R, Hayashi M, Shimizu K, Nakamura N, Tamura T, Yoshizato K. Transgenic silkworms produce recombinant human type III procollagen in cocoons. Nature Biotechnology, 2003, 21(1): 52-56. |
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