• Publications Supported by U.M. Transgenic Core
  • Key Gene Targeting Papers
  • 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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    Key Gene Targeting Papers
    Retrieve Abstracts

    Revised Nomenclature of 129 mouse strains from The Jackson Laboratory.

    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.

    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.

    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.

    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.

    Mansour, SL, Thomas, KR, Deng, CX, Capecchi, MR. 1990. Introduction of a lacZ reporter gene into the mouse int-2 locus by homologous recombination. Proc. Natl. Acad .Sci. U.S.A. 87:7688-7692

    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.

    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.

    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.

    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.

    Thomas, KR, Capecchi, MR. 1987. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:503-512.

    Tybulewicz, VLJ, Crawford, CE, Jackson, PK, Bronson, PT, Mulligan, RC. 1991. Neonatal lethality and lymphopenia in Mice with a homozygous disruption of the c-abl proto-oncogene. Cell 65:1153-1163.

    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.

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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
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    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
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    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
    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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