• Publications Supported by U.M. Transgenic Core
  • C57BL/6 ES Cells and Gene Targeting
  • Key Gene Targeting Papers
  • Engineered Nucleases in Mice and Rats
  • Transgenic Production and Core Facilities
  • Tetracycline Regulated Transgene Expression
  • Mifepristone (RU486) Regulated Transgene Expression
  • Cre-loxP Mediated Gene Manipulation
  • P1 Genomic Clones and Transgenic Mice
  • BAC Transgenic Mice
  • Genomic Sequence Comparisons to Identify Gene Regulatory Elements
  • Review Articles and Books
  • Retrieve Abstracts


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    C57BL/6 ES Cells and Gene Targeting


    Auerbach W, Dunmore JH, Fairchild-Huntress V, Fang Q, Auerbach AB, Huszar D, Joyner AL. 2000. Establishment and chimera analysis of 129/SvEv- and C57BL/6-derived mouse embryonic stem cell lines. Biotechniques. 29:1024-1032.

    Bradley A, Anastassiadis K, Ayadi A, Battey JF, Bell C, Birling MC, Bottomley J, Brown SD, Bürger A, Bult CJ, Bushell W, Collins FS, Desaintes C, Doe B, Economides A, Eppig JT, Finnell RH, Fletcher C, Fray M, Frendewey D, Friedel RH, Grosveld FG, Hansen J, Hérault Y, Hicks G, Hörlein A, Houghton R, Hrabé de Angelis M, Huylebroeck D, Iyer V, de Jong PJ, Kadin JA, Kaloff C, Kennedy K, Koutsourakis M, Lloyd KC, Marschall S, Mason J, McKerlie C, McLeod MP, von Melchner H, Moore M, Mujica AO, Nagy A, Nefedov M, Nutter LM, Pavlovic G, Peterson JL, Pollock J, Ramirez-Solis R, Rancourt DE, Raspa M, Remacle JE, Ringwald M, Rosen B, Rosenthal N, Rossant J, Ruiz Noppinger P, Ryder E, Schick JZ, Schnütgen F, Schofield P, Seisenberger C, Selloum M, Simpson EM, Skarnes WC, Smedley D, Stanford WL, Stewart AF, Stone K, Swan K, Tadepally H, Teboul L, Tocchini-Valentini GP, Valenzuela D, West AP, Yamamura K, Yoshinaga Y, Wurst W. 2012. The mammalian gene function resource: the International Knockout Mouse Consortium. Mamm Genome. 23:580-586.

    Hughes ED, Saunders TL. 2011. “Gene Targeting in Embryonic Stem Cells” in Advanced Protocols for Animal Transgenesis: An ISTT Manual. S Pease and TL Saunders (eds) Springer-Verlag, Berlin. pp. 291-325.

    Hughes ED, Qu YY, Genik SJ, Lyons RH, Pacheco CD, Lieberman AP, Samuelson LC, Nasonkin IO, Camper SA, Van Keuren ML, Saunders TL. 2007. Genetic variation in C57BL/6 ES cell lines and genetic instability in the Bruce4 C57BL/6 ES cell line. Mamm Genome. 18:549-558.


    Kontgen F, Suss G, Stewart C, Steinmetz M, Bluethmann H. 1993. Targeted disruption of the MHC class II Aa gene in C57BL/6 mice. Int Immunol. 5:957-64.

    Kranz A, Fu J, Duerschke K, Weidlich S, Naumann R, Stewart AF, Anastassiadis K. 2010. An improved Flp deleter mouse in C57Bl/6 based on Flpo recombinase. Genesis. 48:512-520.

    Lemckert FA, Sedgwick JD, Körner H. 1997. Gene targeting in C57BL/6 ES cells. Successful germ line transmission using recipient BALB/c blastocysts developmentally matured in vitro. Nucleic Acids Res. 25:917-918.

    Pettitt SJ, Liang Q, Rairdan XY, Moran JL, Prosser HM, Beier DR, Lloyd KC, Bradley A, Skarnes WC. 2009. Agouti C57BL/6N embryonic stem cells for mouse genetic resources. Nat Methods. 6:493-495.

    Poueymirou WT, Auerbach W, Frendewey D, Hickey JF, Escaravage JM, Esau L, Doré AT, Stevens S, Adams NC, Dominguez MG, Gale NW, Yancopoulos GD, DeChiara TM, Valenzuela DM. 2007. F0 generation mice fully derived from gene-targeted embryonic stem cells allowing immediate phenotypic analyses. Nat Biotechnol. 25:91-99.

    Ryder E1, Doe B, Gleeson D, Houghton R, Dalvi P, Grau E, Habib B, Miklejewska E, Newman S, Sethi D, Sinclair C, Vyas S, Wardle-Jones H; Sanger Mouse Genetics Project, Bottomley J, Bussell J, Galli A, Salisbury J, Ramirez-Solis R. 2014. Rapid conversion of EUCOMM/KOMP-CSD alleles in mouse embryos using a cell-permeable Cre recombinase. Transgenic Res. 23:177-185.

    Ryder E, Gleeson D, Sethi D, Vyas S, Miklejewska E, Dalvi P, Habib B, Cook R, Hardy M, Jhaveri K, Bottomley J, Wardle-Jones H, Bussell JN, Houghton R, Salisbury J, Skarnes WC; Sanger Mouse Genetics Project, Ramirez-Solis R. Molecular characterization of mutant mouse strains generated from the EUCOMM/KOMP-CSD ES cell resource. Mamm Genome.24:286-294.

    Saunders, TL. 2011. “Gene Targeting Vector Design for Embryonic Stem Cell Modifications” in Advanced Protocols for Animal Transgenesis: An ISTT Manual. S Pease and TL Saunders (eds) Springer-Verlag, Berlin. pp. 57-79.

    Schuster-Gossler K, Lee AW, Lerner CP, Parker HJ, Dyer VW, Scott VE, Gossler A, Conover JC. 2001. Use of coisogenic host blastocysts for efficient establishment of germline chimeras with C57BL/6J ES cell lines. Biotechniques. 31:1022-1026.

    Seong E, Saunders TL, Stewart CL, Burmeister M.  2004. To knockout in 129 or in C57BL/6: that is the question. Trends Genet.20:59-62.

    Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A. 2011. A conditional knockout resource for the genome-wide study of mouse gene function. Nature. 474:337-342.

    Singla V, Hunkapiller J, Santos N, Seol AD, Norman AR, Wakenight P, Skarnes WC, Reiter JF. 2010. Floxin, a resource for genetically engineering mouse ESCs. Nat Methods. 7:50-52.


    Osterwalder M, Galli A, Rosen B, Skarnes WC, Zeller R, Lopez-Rios J. 2010. Dual RMCE for efficient reengineering of mouse mutant alleles. Nat Methods. 7:893-895.


    Key Gene Targeting Papers
    Retrieve Abstracts

    Revised Nomenclature of 129 mouse strains from The Jackson Laboratory.

    Doetschman, TC, Eistetter, H, Katz, M, Schmidt, W, Kemler, R. 1985. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J. Embryol. Exp. Morphol. 87:27-45.


    Fedorov LM, Haegel-Kronenberger H, Hirchenhain J. 1997. A comparison of the germline potential of differently aged ES cell lines and their transfected descendants. Transgenic Res. 6:223-31.

    George SH, Gertsenstein M, Vintersten K, Korets-Smith E, Murphy J, Stevens ME, Haigh JJ, Nagy A. 2007. Developmental and adult phenotyping directly from mutant embryonic stem cells. Proc Natl Acad Sci U S A. 104:4455-60.

    Liu X, Wu H, Loring J, Hormuzdi S, Disteche CM, Bornstein P, Jaenisch R. 1997. Trisomy eight in ES cells is a common potential problem in gene targeting and interferes with germ line transmission. Dev Dyn. 209:85-91.

    Longo L, Bygrave A, Grosveld FG, Pandolfi PP. 1997. The chromosome make-up of mouse embryonic stem cells is predictive of somatic and germ cell chimaerism. Transgenic Res. 6:321-328.

    McMahon AP, Bradley A.1990. The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain.Cell. 62:1073-85.

    Nagy A. Cre recombinase: the universal reagent for genome tailoring. Genesis. 2000 Feb;26(2):99-109. Download This Paper.

    Nagy A, Rossant J, Nagy R, Abramow-Newerly W, Roder JC. 1993. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc. Natl. Acad. Sci. U.S.A. 90:8424-8428.

    Ramirez-Solis R, Rivera-Perez J, Wallace JD, Wims M, Zheng H, Bradley A. 1992. Genomic DNA microextraction: a method to screen numerous samples. Anal Biochem.  201(2):331-5.

    Rebuzzini P, Neri T, Mazzini G, Zuccotti M, Redi CA, Garagna S. 2008. Karyotype analysis of the euploid cell population of a mouse embryonic stem cell line revealed a high incidence of chromosome abnormalities that varied during culture. Cytogenet Genome Res. 121:18-24.

    Simpson EM, Linder CC, Sargent EE, Davisson MT, Mobraaten LE, Sharp JJ. 1997. Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice. Nat. Genet. 16:19-27.

    Schnutgen F, De-Zolt S, Van Sloun P, Hollatz M, Floss T, Hansen J, Altschmied J, Seisenberger C, Ghyselinck NB, Ruiz P, Chambon P, Wurst W, von Melchner H. 2005. Genomewide production of multipurpose alleles for the functional analysis of the mouse genome. Proc Natl Acad Sci U S A. 102:7221-6.

    Sugawara A, Goto K, Sotomaru Y, Sofuni T, Ito T. 2006. Current status of chromosomal abnormalities in mouse embryonic stem cell lines used in Japan. Comp Med. 56:31-34
    .

    Swiatek, PJ, and Gridley T. 1993. Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20. Genes and Develop. 7:2071-2084.

    te Riele, H, Maandag, ER, Berns, A. 1992. Highly efficient gene targeting in embryonic stem cells through homologous recombination with isogenic DNA constructs. Proc. Natl. Acad .Sci. U.S.A. 89:5128-5132.

    Threadgill DW, Yee D, Matin A, Nadeau JH, Magnuson T. 1997 Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain. Mamm Genome. 8:390-3.

    van Deursen J, Wieringa B. Targeting of the creatine kinase M gene in embryonic stem cells using isogenic and nonisogenic vectors. 1992. Nucleic Acids Res. 20:3815-3820.

    Zhou L, Rowley DL, Mi QS, Sefcovic N, Matthes HW, Kieffer BL, Donovan DM. Murine inter-strain polymorphisms alter gene targeting frequencies at the mu opioid receptor locus in embryonic stem cells. Mamm Genome. 2001 Oct;12(10):772-8.

    Chen L, Adar R, Yang X, Monsonego EO, Li C, Hauschka PV, Yayon A, Deng CX. 1999. Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. J Clin Invest 104:1517–1525.

    Fiering S, Epner E, Robinson K, Zhuang Y, Telling A, Hu M, Martin DIK, 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 and Development 9:2203-2213.

    Meyers EN, Lewandoski M, Martin GR. 1998. An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination. Nat Genet. 18:136-41.

    Nagy A, Moens C, Ivanyi E, Pawling J, Gertsenstein M, Hadjantonakis AK, Pirity M, Rossant J. 1998. Dissecting the role of N-myc in development using a single targetiing vector to generate a series of alleles. Curr Biol. 1998 May 21;8(11):661-4.

    Olson EN, Arnold HH, Rigby PW, Wold BJ. 1996. Know your neighbors: three phenotypes in null mutants of the myogenic bHLH gene MRF4. Cell. 85:1-4.

    Rucker EB 3rd, Dierisseau P, Wagner KU, Garrett L, Wynshaw-Boris A, Flaws JA, Hennighausen L. 2000. Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol Endocrinol 14:1038–1052.

    Scacheri PC, Crabtree JS, Novotny EA, Garrett-Beal L, Chen A, Edgemon KA, Marx SJ, Spiegel AM, Chandrasekharappa SC, Collins FS. 2001. Bidirectional transcriptional activity of PGK-neomycin and unexpected embryonic lethality in heterozygote chimeric knockout mice. Genesis. 30:259-63.

    Xu X, Wagner KU, Larson D, Weaver Z, Li C, Ried T, Hennighausen L, Wynshaw-Boris A, Deng CX. 1999. Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat Genet. 22:37-43.


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    Engineered Nuclease Modified Mice and Rats
    ZFN Rat Knockout Models from the Rat Genome Database
    Rat Knockout Models at the Knock Out Rat Consortium

    Bedell VM, Wang Y, Campbell JM, Poshusta TL, Starker CG, Krug RG 2nd, Tan W, Penheiter SG, Ma AC, Leung AY, Fahrenkrug SC, Carlson DF, Voytas DF, Clark KJ, Essner JJ, Ekker SC. 2012. In vivo genome editing using a high-efficiency TALEN system. Nature. 491:114-118.

    Brown AJ, Fisher DA, Kouranova E, McCoy A, Forbes K, Wu Y, Henry R, Ji D, Chambers A, Warren J, Shu W, Weinstein EJ, Cui X. 2013. Whole-rat conditional gene knockout via genome editing. Nat Methods. 10:638-640.

    Carbery ID, Ji D, Harrington A, Brown V, Weinstein EJ, Liaw L, Cui X. 2010. Targeted genome modification in mice using zinc-finger nucleases. Genetics. 186:451-459.

    Chen F, Pruett-Miller SM, Huang Y, Gjoka M, Duda K, Taunton J, Collingwood TN, Frodin M, Davis GD. 2011. High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases. Nat Methods. 8:753-755.

    Cheng AW, Wang H, Yang H, Shi L, Katz Y, Theunissen TW, Rangarajan S, Shivalila CS, Dadon DB, Jaenisch R. 2013. Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell Res. 2013 Aug 27. doi: 10.1038/cr.2013.122. [Epub ahead of print]

    Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F. 2013. Multiplex Genome Engineering Using CRISPR/Cas Systems. Science. 339:819-823.

    Cui X, Ji D, Fisher DA, Wu Y, Briner DM, Weinstein EJ. 2011. Targeted integration in rat and mouse embryos with zinc-finger nucleases.  Nat Biotechnol. 29:64-67.

    Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD. 2013. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol. 31:822-826.

    Fujii W, Kawasaki K, Sugiura K, Naito K. 2013. Efficient generation of large-scale genome-modified mice using gRNA and CAS9 endonuclease. Nucleic Acids Res. 41:e187.

    Fujii W, Onuma A, Sugiura K, Naito K. 2014. Efficient generation of genome-modified mice via offset-nicking by CRISPR/Cas system. Biochem Biophys Res Commun. 445:791-794.

    Gennequin B, Otte DM, Zimmer A. 2013. CRISPR/Cas-induced double-strand breaks boost the frequency of gene replacements for humanizing the mouse Cnr2 gene. Biochem Biophys Res Commun. 441:815-819.

    Geurts AM, Cost GJ, Freyvert Y, Zeitler B, Miller JC, Choi VM, Jenkins SS, Wood A, Cui X, Meng X, Vincent A, Lam S, Michalkiewicz M, Schilling R, Foeckler J, Kalloway S, Weiler H, Ménoret S, Anegon I, Davis GD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jacob HJ, Buelow R. 2009. Knockout rats via embryo microinjection of zinc-finger nucleases. Science. 325:433.


    Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, Guimaraes C, Panning B, Ploegh HL, Bassik MC, Qi LS, Kampmann M, Weissman JS. 2014. Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation. Cell. 2014 Oct 8. pii: S0092-8674(14)01178-7. doi: 10.1016/j.cell.2014.09.029. [Epub ahead of print]

    Horii T, Arai Y, Yamazaki M, Morita S, Kimura M, Itoh M, Abe Y, Hatada I. 2014. Validation of microinjection methods for generating knockout mice by CRISPR/Cas-mediated genome engineering. Sci Rep. 4:4513.

    Jones JM, Meisler MH. 2014. Modeling human epilepsy by TALEN targeting of mouse sodium channel Scn8a. Genesis. 52:141-148.

    Joung JK, Sander JD. 2013. TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol. 14:49-55.


    Li C, Qi R, Singleterry R, Hyle J, Balch A, Li X, Sublett J, Berns H, Valentine M, Valentine V, Sherr CJ. 2014. Simultaneous Gene Editing by Injection of mRNAs Encoding Transcription Activator-Like Effector Nucleases (TALENS) into Mouse Zygotes. Mol Cell Biol. 2014 Feb 24. [Epub ahead of print]

    Li D, Qiu Z, Shao Y, Chen Y, Guan Y, Liu M, Li Y, Gao N, Wang L, Lu X, Zhao Y, Liu M. 2013. Heritable gene targeting in the mouse and rat using a CRISPR-Cas system. Nat Biotechnol. 31:681-683.

    Li W, Teng F, Li T, Zhou Q. 2013. Simultaneous generation and germline transmission of multiple gene mutations in rat using CRISPR-Cas systems. Nat Biotechnol. 31:684-686.

    Mali P, Aach J, Stranges PB, Esvelt KM, Moosburner M, Kosuri S, Yang L, Church GM. 2013. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat Biotechnol. 31:833-838.

    Mali P, Yang L, Esvelt KM, Aach J, Guell M, Dicarlo JE, Norville JE, Church GM. 2013. RNA-Guided Human Genome Engineering via Cas9. Science. 339:823-826.

    Mashiko D, Fujihara Y, Satouh Y, Miyata H, Isotani A, Ikawa M. 2013 Generation of mutant mice by pronuclear injection of circular plasmid expressing Cas9 and single guided RNA. Sci Rep. 3:3355.

    Mashiko D, Young SA, Muto M, Kato H, Nozawa K, Ogawa M, Noda T, Kim YJ, Satouh Y, Fujihara Y, Ikawa M. 2014. Feasibility for a large scale mouse mutagenesis by injecting CRISPR/Cas plasmid into zygotes. Dev Growth Differ. 56:122-129.

    Ma Y, Zhang X, Shen B, Lu Y, Chen W, Ma J, Bai L, Huang X, Zhang L. 2014. Generating rats with conditional alleles using CRISPR/Cas9. Cell Res. 24:122-125.

    Ménoret S, Fontanière S, Jantz D, Tesson L, Thinard R, Rémy S, Usal C, Ouisse LH, Fraichard A, Anegon I. 2013. Generation of Rag1-knockout immunodeficient rats and mice using engineered meganucleases. FASEB J. 27:703-711.


    Meyer M, de Angelis MH, Wurst W, Kühn R. 2010. Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases. Proc Natl Acad Sci U S A. 107:15022-6.

    Meyer M, Ortiz O, Hrabé de Angelis M, Wurst W, Kühn R. 2012. Modeling disease mutations by gene targeting in one-cell mouse embryos. Proc Natl Acad Sci U S A. 109:9354-9359.

    Pattanayak V, Lin S, Guilinger JP, Ma E, Doudna JA, Liu DR. 2013. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat Biotechnol. 31:839-843.

    Ran FA, Hsu PD, Lin CY, Gootenberg JS, Konermann S, Trevino AE, Scott DA, Inoue A, Matoba S, Zhang Y, Zhang F. 2013. Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity. Cell. 154:1380-1389.

    Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. 2013. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 8:2281-2308.

    Shen B, Zhang W, Zhang J, Zhou J, Wang J, Chen L, Wang L, Hodgkins A, Iyer V, Huang X, Skarnes WC. 2014. Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects. Nat. Methods. 11: 399-402.

    Shen B, Zhang J, Wu H, Wang J, Ma K, Li Z, Zhang X, Zhang P, Huang X. 2013 Generation of gene-modified mice via Cas9/RNA-mediated gene targeting.. Cell Res. 23:720-723.


    Singh P, Schimenti JC, Bolcun-Filas E. 2014. A Mouse Geneticist's Practical Guide to CRISPR Applications. Genetics. 2014 Sep 29. pii: genetics.114.169771. [Epub ahead of print]

    Srivastava M, Nambiar M, Sharma S, Karki SS, Goldsmith G, Hegde M, Kumar S, Pandey M, Singh RK, Ray P, Natarajan R, Kelkar M, De A, Choudhary B, Raghavan SC. 2012. An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell. 151:1474-1487.

    Sung YH, Baek IJ, Kim DH, Jeon J, Lee J, Lee K, Jeong D, Kim JS, Lee HW. 2013. Knockout mice created by TALEN-mediated gene targeting. Nat Biotechnol. 31:23-24.

    Tesson L, Usal C, Ménoret S, Leung E, Niles BJ, Remy S, Santiago Y, Vincent AI, Meng X, Zhang L, Gregory PD, Anegon I, Cost GJ. 2011. Knockout rats generated by embryo microinjection of TALENs. Nat Biotechnol. 29:695-696.

    Tsai SQ, Wyvekens N, Khayter C, Foden JA, Thapar V, Reyon D, Goodwin MJ, Aryee MJ, Joung JK. 2014. Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nature Biotechnology. published online 25 April 2014. doi:10.1038/nbt.2908

    Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R. 2013. One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering. Cell. 153:910-918.

    Wefers B, Meyer M, Ortiz O, Hrabé de Angelis M, Hansen J, Wurst W, Kühn R. 2013. Direct production of mouse disease models by embryo microinjection of TALENs and oli godeoxynucleotides. Proc Natl Acad Sci U S A. 110:3782-3787.

    Wefers B, Panda SK, Ortiz O, Brandl C, Hensler S, Hansen J, Wurst W, Kühn R. 2013. Generation of targeted mouse mutants by embryo microinjection of TALEN mRNA. Nat Protoc. 8:2355-2379.

    Yang H, Wang H, Shivalila CS, Cheng AW, Shi L, Jaenisch R. 2013. One-Step Generation of Mice Carrying Reporter and Conditional Alleles by CRISPR/Cas-Mediated Genome Engineering. Cell. 154:1370-1379.



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    Transgenic Production & Core Facilities

    Auerbach AB, Norinsky R, Ho W, Losos K, Guo Q, Chatterjee S, Joyner AL. 2003. Strain-dependent differences in the efficiency of transgenic mouse production. Transgenic Res. 12:59-69.

    Brinster RL, Chen HY, Trumbauer ME, Yagle MK, Palmiter RD. 1985. Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. Proc Natl Acad Sci U S A. 82:4438-4442.

    De Paoli P. 2009. Institutional shared resources and translational cancer research. J Transl Med. 7:54.

    Farber GK, Weiss L. 2011.  Core facilities: maximizing the return on investment. Sci Transl Med. 3:95cm21.

    Fielder TJ, Barrios L, Montoliu L. 2010. A survey to establish performance standards for the production of transgenic mice. Transgenic Res. 19:675-81.

    Fielder, TJ, Montoliu L. 2011. Transgenic Production Benchmarks. in Advanced Protocols for Animal Transgenesis: An ISTT Manual. Pease S, Saunders TL (eds). Springer-Verlag, Berlin. pp. 81-97.

    Loomis CA, Curchoe CL. 2012. Method for tracking core-contributed publications. J Biomol Tech. 23:122-127.


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    Tetracycline Regulated Transgene Expression
    Methodology
    Prof. Dr. Hermann Bujard's Website on Tetracycline Controlled Transcriptional Activation
    NIH Mammary Gland Biology Website
    in vivo Applications
    in vitro Applications

    Methodology
    Retrieve Abstracts

    Furth, PA, St Onge, L, Boger, H, Gruss, P, Gossen, M, Kistner, A, Bujard, H, Hennighausen, L. 1994. Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc. Natl. Acad. Sci. U.S.A. 91:9302-9306.

    Gill, G, Ptashne, M. 1988. Negative effect of the transcriptional activator GAL4. Nature. 334:721-723.

    Kistner, A, Gossen M, Zimmermann, F, Jerecic, J, Ullmer, C, Lubbbert, H, Bujard, H. 1996. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 93:10933-10938.

    Passman, RS, Fishman, GI. 1994. Regulated expression of foreign genes in vivo after germline transfer. J. Clin. Invest.94:2421-2425.

    Schultze, N, Burki, Y, Lang Y, Certa, U, Bluethmann, H. 1996. Efficient Control of gene expression by single step integration of the tetracycline system in transgenic mice. Nature Biotechnology. 14:499-503.

    Shockett, P, Difilippantonio, M, Hellman, N, Schatz, DG. 1995. A modified tetracycline-regulated system provides autoregulatory, inducible gene expression in cultured cells and transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 92:6522-6526.

    St-Onge, L, Furth, PA, Gruss, P. 1996. Temporal control of the Cre recombinase in transgenic mice by a tetracycline responsive promoter. Nucl. Acids Res. 24:3875-3877.

    Yu Z, Redfern CS, Fishman GI. 1996. Conditional transgene expression in the heart. Circ. Res. 79:691-697.

    in vivo Applications
    Retrieve Abstracts

    Dhawan, J, Rando, TA, Elson, SL, Bujard, H, Blau, HM. 1995. Tetracycline-regulated gene expression following direct gene transfer into mouse skeletal muscle. Somat Cell Mol Genet 21:233-240.

    Efrat, S, Fusco-DeMane, D, Lemberg, H, al Emran, O, Wang, X. 1995. Conditional transformation of a pancreatic beta-cell line derived from transgenic mice expressing a tetracycline-regulated oncogene. Proc. Natl. Acad. Sci. U.S.A. 92:3576-3580.

    Ewald, D, Li, M, Efrat, S, Auer, G, Wall, RJ, Furth, PA, Hennighausen, L. 1996. Time-sensitive reversal of hyperplasia in transgenic mice expressing SV40 T antigen. Science. 273:1384-1386.

    Hennighausen, L, Wall, RJ, Tillmann, U, Li, M, Furth, PA. 1995. Conditional gene expression in secretory tissues and skin of transgenic mice using the MMTV-LTR and the tetracycline responsive system. J. Cell. Biochem. 59:463-472.

    Mayford, M, Bach, ME, Huang, YY, Wang, L, Hawkins, RD, Kandel, ER. 1996. Control of memory formation through regulated expression of a CaMKII transgene. Science 274:1678-1683.

    in vitro Applications
    Retrieve Abstracts

    Ackland-Berglund, CE, Leib, DA. 1995. Efficacy of tetracycline-controlled gene expression is influenced by cell type. Biotechniques. 18:196-200.

    Gossen, M, Bujard, H. Tight control of gene expression in mammalian cells by tetetracycline-responsive promoters. Proc. Natl. Acad. Sci. U.S.A. 89:5547-5551.

    Gossen, M, Freundlieb, S, Bender, G, Muller, G, Hillen, W, Bujard, H. 1995. Transcriptional activation by tetracyclines in mammalian cells. Science, 268:1766-1769.

    Deuschle, U, Meyer, WK, Thiesen, HJ. 1995. Tetracycline-reversible silencing of eukaryotic promoters. Mol. Cell. Biol. 15:1907-1914.

    Hofmann, A, Nolan, GP, Blau, HM. 1996. Rapid retroviral delivery of tetracycline-inducible genes in a single autoregulatory cassette. Proc. Natl. Acad. Sci. U.S.A. 93:5185-5190.


    Mifepristone (RU486) Regulated Transgene Expression

    Wang, Y, Xu, J, Pierson, T, O'Malley, BW, Tsai, SY. 1997. Positive and negative regulation of gene expression in eukaryotic cells with an inducible transcriptional regulator. Gene Ther. 4:432-441.

    Wang Y, DeMayo FJ, Tsai SY, O'Malley BW. 1997. Ligand-inducible and liver-specific target gene expression in transgenic mice. Nat. Biotechnol. 15:239-243.

    Wang Y, O'Malley BW, Tsai SY. 1997. Inducible system designed for future gene therapy. Methods Mol. Biol. 63:401-413.

    Wang Y, O'Malley BW Jr, Tsai SY, O'Malley BW. 1994. A regulatory system for use in gene transfer. Proc. Natl. Acad. Sci. U S A 91:8180-8184.


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    Cre-loxP Mediated Gene Manipulation
    Methodology
    Andras Nagy's Website Cre Transgenic Database
    NIH Mammary Gland Biology Website
    in vivo Applications

    Methodology
    Retrieve Abstracts

        Transient Cre Expression  
    Araki, K, Araki, M, Miyazaki, J, Vassalli, P. 1995. Site-specific recombination of a transgene in fertilized eggs by transient expression of Cre
    recombinase. Proc. Natl. Acad. Sci. U.S.A. 92:160-164.

    de Wit T, Drabek D, Grosveld F. 1998. Microinjection of cre recombinase RNA induces site-specific recombination of a transgene in mouse oocytes. Nucleic Acids Res. 26:676-678.

    Kaartinen V, Nagy A.  2001. Removal of the floxed neo gene from a conditional knockout allele by the adenoviral Cre recombinase in vivo. Genesis. 31:126-129.

    Lauth M, Moerl K, Barski JJ, Meyer M. 2000. Characterization of Cre-mediated cassette exchange after plasmid microinjection in fertilized mouse oocytes. Genesis. 27:153-8.

    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 U S A. 299:4489-4494.

    Sato M, Yasuoka Y, Kodama H, Watanabe T, Miyazaki JI, Kimura M. 2000. New approach to cell lineage analysis in mammals using the Cre-loxP system. Mol Reprod Dev. 56:34-44.

    Stecca B, Southwood CM, Gragerov A, Kelley KA, Friedrich VL Jr, Gow A. 2000. The evolution of lipophilin genes from invertebrates to tetrapods: DM-20 cannot replace proteolipid protein in CNS myelin. J Neurosci. 20:4002-4010. 

    Sunaga S, Maki K, Komagata Y, Ikuta K, Miyazaki JI. 1997. 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.

    Xu X, Li C, Garrett-Beal L, Larson D, Wynshaw-Boris A, Deng CX. 2001. Direct removal in the mouse of a floxed neo gene from a three-loxP conditional knockout allele by two novel approaches. Genesis. 30:1-6.

        Proof of Principle  
    Kuhn, R, Schwenk, F, Aguet, M, Rajewsky, K. 1995 . Inducible gene targeting in mice. Science 269:1427-1429.

    Lasko, M, Pichel, JG, Gorman, JR, Sauer, B, Okamoto, Y, Lee, E, Alt, FW, Westphal, H. 1996. Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc. Natl. Acad. Sci. U.S.A. 93:5860-5865.

    Orban, PC, Chui, D, Marth, JD. 1992. Tissue- and site-specific DNA recombination in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 89:6861-6865.

    Sauer B. 1993. Manipulation of transgenes by site-specific recombination: use of Cre recombinase Methods Enzymol. 225:890-900.

    Schwenk, F, Baron, U, Rajewsky, K. 1995. A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells. Nucl. Acids Res. 23:5080-5081.

    Sunaga, S, Maki, K, Komagata, Y, Ikuta, K, Miyazaki, JI. 1997. 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.

    in vivo Applications
    Retrieve Abstracts

    Betz, UA, Vosshenrich, CA, Rajewsky, K, Muller, W. 1996. Bypass of lethality with mosaic mice generated by Cre-loxP-mediated recombination. Curr. Biol. 6:1307-1316.

    Brooks, AI, Muhkerjee, B, Panahian, N, Cory-Slechta, D, Federoff, HJ.1997. Nerve growth factor somatic mosaicism produced by herpes virus-directed expression of cre recombinase. Nat. Biotechnol. 15:57-62.

    Feil, R, Brocard, J, Mascrez, B, LeMeur, M, Metzger, D, Chambon, P. 1996. Ligand-activated site-specific recombination in mice. Proc. Natl. Acad. Sci. U.S.A. 93:10887-10890.

    Gu, H, Marth, JD, Orban, PC, Mossmann, H, Rajewsky, K. 1994. Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science. 265:103-106.

    Hennet ,T, Hagen, FK, Tabak, LA, Marth, JD. 1995. T-cell-specific deletion of a polypeptide N-acetylgalactosaminyl-transferase gene by site-directed recombination. Proc. Natl. Acad. Sci. U.S.A. 92 :12070-12074

    Kitamoto, T, Nakamura, K, Nakao, K, Shibuya, S, Shin, RW, Gondo, Y, Katsuki, M, Tateishi, J. 1996.Humanized prion protein knock-in by Cre-induced site-specific recombination in the mouse. Biochem Biophys. Res. Comm. 222:742-747.

    Lakso, M, Sauer, B, Mosinger B Jr, Lee, EJ, Manning, RW, Yu, SH, Mulder, KL, Westphal, H. 1992. Targeted oncogene activation by site-specific recombination in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 89:6232-6236.

    Lewandosk,i M, Wassarman KM, Martin, GR. 1997. Zp3-cre, a transgenic mouse line for the activation or inactivation of loxP-flanked target genes specifically in the female germ line. Curr. Biol. 7:148-151.

    Pichel, JG, Lakso, M, Westphal, H. 1993. Timing of SV40 oncogene activation by site-specific recombination determines subsequent tumor progression during murine lens development. Oncogene. 8:3333-8342.

    St-Onge, L, Furth, PA, Gruss, P. 1996. Temporal control of the Cre recombinase in transgenic mice by a tetracycline responsive promoter. Nucl. Acids Res. 24:3875-3877.

    Tsien, JZ, Chen, DF, Gerber, D, Tom, C, Mercer, EH, Anderson, DJ, Mayford, M, Kandel, ER, Tonegawa, S.1996. Subregion- and cell type-restricted gene knockout in mouse brain. Cell 87:1317-1326.

    Wang, Y, Krushel, LA, Edelman, GM. 1996. Targeted DNA recombination in vivo using an adenovirus carrying the cre recombinase gene. Proc. Natl. Acad. Sci. U.S.A. 3:3932-3936.

    Zhang Y, Riesterer C, Ayrall AM, Sablitzky F, Littlewood TD, Reth M. 1996. Inducible site-directed recombination in mouse embryonic stem cells. Nucl. Acids Res. 24:543-548.


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    P1 Genomic Clones and Transgenic Mice
    Retrieve Abstracts
     

    Callow MJ, Stoltzfus LJ, Lawn RM, Rubin EM. 1994. Expression of human apolipoprotein B and assembly of lipoprotein(a) in transgenic mice. Proc. Natl. Acad .Sci. U.S.A. 91:2130-2134.

    Linton, MF, Farese, RV Jr, Chiesa, G, Grass, DS, Chin, P, Hammer, RE, Hobbs, HH, Young, SG. 1993. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a). J. Clin. Invest. 92:3029-3037.

    Liu, C, Yu K, Shen, K, Liu Z, Noguchi, CT. 1996. Transgenic mice containing the human erythropoietin receptor gene exhibit correct hematopoietic and neural expression. Proc Assoc Am Physicians 108:449-454.

    McCormick, SP, Linton, MF, Young, SG. 1994. Expression of P1 DNA in mammalian cells and transgenic mice. Genet Anal Tech Appl 11:158-164

    McCormick, SP, Ng, JK, Veniant, M, Boren, J, Pierotti, V, Flynn, LM, Grass, DS, Connolly, A, Young, SG. 1996. Transgenic mice that overexpress mouse apolipoprotein B. Evidence that the DNA sequences controlling intestinal expression of the apolipoprotein B gene are distant from the structural gene. Biol. Chem. 271:11963-11970.

    Smith DJ, Zhu Y, Zhang J, Cheng JF, Rubin EM. 1995. Construction of a panel of transgenic mice containing a contiguous 2-Mb set of YAC/P1 clones from human chromosome 21q22.2. Genomics 27:425-434.

    Wagner, SD, Gross, G, Cook, GP, Davies, SL, Neuberger, MS. 1996. Antibody expression from the core region of the human IgH locus reconstructed in transgenic mice using bacteriophage P1 clones. Genomics 35:405-414.


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    BAC Transgenic Mice

    Van Keuren ML, Gavrilina GB, Filipiak WE, Zeidler MG, Saunders TL.2009. Generating transgenic mice from bacterial artificial chromosomes: transgenesis efficiency, integration and expression outcomes. Transgenic Res. 18:769-785.

    Chiang C, Jacobsen JC, Ernst C, Hanscom C, Heilbut A, Blumenthal I, Mills RE, Kirby A, Lindgren AM, Rudiger SR, McLaughlan CJ, Bawden CS, Reid SJ, Faull RL, Snell RG, Hall IM, Shen Y, Ohsumi TK, Borowsky ML, Daly MJ, Lee C, Morton CC, MacDonald ME, Gusella JF, Talkowski ME. 2012. Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nat Genet. 44:390-397.

    Dubose AJ, Lichtenstein ST, Narisu N, Bonnycastle LL, Swift AJ, Chines PS, Collins FS. 2013. Use of microarray hybrid capture and next-generation sequencing to identify the anatomy of a transgene. Nucleic Acids Res. 41(6):e70.

    Zeidler MG, Van Keuren ML, Saunders TL. 2011. “BAC Transgenes, DNA Purification, and Transgenic Mouse Production” in Advanced Protocols for Animal Transgenesis: An ISTT Manual. S Pease and TL Saunders (eds) Springer-Verlag, Berlin. pp. 159-179.

    Retrieve Abstracts

    Retrofitting of PACs and BACs

    Antoch, MP, Song, EJ, Chang, AM, Vitaterna, MH, Zhao, Y, Wilsbacher, LD, Sangoram, AM, King, DP, Pinto, LH, Takahashi, JS. 1997. Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell 89:655-667.

    Chrast R, Scott HS, Antonarakis SE Linearization and purification of BAC DNA for the development of transgenic mice. Transgenic Res 1999 Apr;8(2):147-50. (Note that the methods in this paper are more time-intensive that those described on this website.)

    Kim, S, Horrigan, S, Altenhofen, J, Arbieva, Z, Hoffman, R, Westbrook, C. 1998. Modification of bacterial artificial chromosome clones using Cre recombinase: Introduction of selectable markers for expression in eukaryotic cells. Genome Research 8:404-412.

    Kim, UJ, Birren, BW, Slepak, T, Mancino, V, Boysen, C, Kang, HL, Simon, MI, Shizuya, H. 1996. Construction and characterization of a human bacterial artificial chromosome library. Genomics 34:213-218.

    Lee JT, Lu N, Han Y . Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain. Proc Natl Acad Sci U S A 1999 Mar 30;96(7):3836-41

    Mullins, LJ, Kotelevtseva, N, Boyd, AC, Mullins, JJ. 1997. Efficient Cre-lox linearisation of BACs: applications to physical mapping and generation of transgenic animals. Nucleic Acids Res. 25:2539-2540.

    Nielsen, LB, McCormick, SP, Pierotti, V, Tam, C, Gunn, MD, Shizuya, H, Young, SG. 1997. Human apolipoprotein B transgenic mice generated with 207- and 145-kilobase pair bacterial artificial chromosomes. Evidence that a distant 5'-element confers appropriate transgene expression in the intestine. J. Biol. Chem. 272:29752-29758.

    Nielsen LB, McCormick SP, Young SG A new approach for studying gene regulation by distant DNA elements in transgenic mice. Scand J Clin Lab Invest Suppl 1999;229:33-9

    Probst, FJ, Fridell, RA, Raphael, Y, Saunders, TL,Wang, A,Liang, Y, Morell, RJ, Touchman, JW, Lyons, RH, Noben-Trauth, K, Friedman, TB, Sally A. Camper, SA. 1998. Correction of Deafness in shaker-2 Mice by an Unconventional Myosin in a BAC Transgene. Science. 280:1447 - 1451.

    Xu, J, Yang, D, Domingo, J, Ni, J, Huang, N. 1998. Screening for overlapping bacterial artificial chromosome clones by PCR analysis with an arbitrary primer. Proc. Natl. Acad. Sci. 95: 5661-5666.

    Yang XW, Model P, Heintz N. 1997. Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome. Nat. Biotechnol. 15:859-865.

    Yang XW, Wynder C, Doughty ML, Heintz N BAC-mediated gene-dosage analysis reveals a role for Zipro1 (Ru49/Zfp38) in progenitor cell proliferation in cerebellum and skin. Nat Genet 1999 Aug;22(4):327-35

    Yu W, Misulovin Z, Suh H, Hardy RR, Jankovic M, Yannoutsos N, Nussenzweig MC. Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5' of RAG2. Science 1999 Aug 13;285(5430):1080-4.


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    Genomic Sequence Comparisons to Identify Gene Regulatory Elements
    Retrieve Abstracts

    Vista Genome Browser Software for Making Cross Species Genome Comparisons.

    Loots GG, Locksley RM, Blankespoor CM, Wang ZE, Miller W, Rubin EM, Frazer KA. 2000. Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science.288:136-40.

    Dubchak I, Brudno M, Loots GG, Pachter L, Mayor C, Rubin EM, Frazer KA. 2000. Active conservation of noncoding sequences revealed by three-way species comparisons. Genome Res. 10:1304-6.

    Touchman JW, Dehejia A, Chiba-Falek O, Cabin DE, Schwartz JR, Orrison BM, Polymeropoulos MH, Nussbaum RL.2001. Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element. Genome Res. 11:78-86.

    Jareborg N, Durbin R. Alfresco--a workbench for comparative genomic sequence analysis. 2001. Genome Res. 10:1148-57.

    Jareborg N, Birney E, Durbin R. 1999. Comparative analysis of noncoding regions of 77 orthologous mouse and human gene pairs. Genome Res. 9:815-24.


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