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Engineering the Mouse Genome to Model Human Disease for Drug Discovery

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Mouse Models for Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 602))

Abstract

Genetically engineered mice (GEM) have become invaluable tools for human disease modeling and drug development. Completion of the mouse genome sequence in combination with transgenesis and gene targeting in embryonal stem cells have opened up unprecedented opportunities. Advanced technologies for derivation of GEM models will be introduced and discussed.

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References

  1. Driscoll, C.A., Menotti-Raymond, M., Roca, A.L., Hupe, K., Johnson, W.E., Geffen, E., Harley, E.H., Delibes, M., Pontier, D., Kitchener, A.C., Yamaguchi, N., O’Brien, S.J., and Macdonald, D.W. (2007) The Near Eastern origin of cat domestication. Science 317, 519–523.

    Article  PubMed  CAS  Google Scholar 

  2. Paigen, K. One hundred years of mouse genetics: an intellectual history. I. The classical period (1902-1980). Genetics 163, 1–7.

    Google Scholar 

  3. Cuenot, L. (1902) La loi de Mendel et l’heredite de la pigmentation chez les souris. Arch. Zool. Exp. Gen. 3, 27–30.

    Google Scholar 

  4. Van Dyke, T. and Jacks, T. (2002) Cancer modeling in the modern era: progress and challenges. Cell 108, 5–15.

    Article  Google Scholar 

  5. Paigen, K. One hundred years of mouse genetics: an intellectual history. II. The molecular revolution (1981-2002). Genetics 163, 1227–1235.

    Google Scholar 

  6. Gordon, J.W., Scangos, G.A., Plotkin, D.J., Barbosa, J.A., and Ruddle, F.H. (1980) Genetic transformation of mouse embryos by microinjection of purified DNA. Proc. Natl. Acad. Sci. USA 77, 7380–7384.

    Article  PubMed  CAS  Google Scholar 

  7. Brinster, R.L., Chen, H.Y., Trumbauer, M., Senear, A.W., Warren, R., and Palmiter, R.D. (1981) Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Cell 27, 223–231.

    Article  PubMed  CAS  Google Scholar 

  8. Constantini, F. and Lacy, E. (1981) Introduction of a rabbit beta-globin gene into the mouse germ line. Nature 294, 92–94.

    Article  Google Scholar 

  9. Harbers, K., Jahner, D., and Jaenisch, R. (1981) Microinjection of cloned viral genomes into mouse zygotes: integration and expression in the animal. Nature 293, 540–542.

    Article  PubMed  CAS  Google Scholar 

  10. Wagner, T.E., Hoppe, P.C., Jollick, J.D., Scholl, D.R., Hodinka, R.L., and Gault, J.B. (1981) Microinjection of a rabbit beta-globin gene into zygotes and its subsequent expression in adult mice and their offspring. Proc. Natl. Acad. Sci. USA 78, 6376–6380.

    Article  PubMed  CAS  Google Scholar 

  11. Jaenisch, R. (1988) Transgenic animals. Science 240, 1468–1474.

    Article  PubMed  CAS  Google Scholar 

  12. Greenberg, N.M., DeMayo, F.J., Finegold, M.J., Medina, D., Tilley, W.D., Aspinall, J.O., Cunha, G.R., Donjacour, A.A., Matusik, R.J., and Rosen, J.M. (1995) Prostate cancer in a transgenic mouse. Proc. Natl. Acad. Sci. USA 92, 3439–3443.

    Article  PubMed  CAS  Google Scholar 

  13. Gingrich, J.R., Barrios, R.J., Morton, R.A., Boyce, B.F., DeMayo, F.J., Finegold, M.J., Angelopoulou, R., Rosen, J.M., and Greenberg, N.M. (1996) Metastatic prostate cancer in a transgenic mouse. Cancer Res. 56, 4096–4102.

    PubMed  CAS  Google Scholar 

  14. Kaplan-Lefko, P.J., Chen, T.M., Ittmann, M.M., Barrios, R.J., Ayala, G.E., Huss, W.J., Maddison, L.A., Foster, B.A., and Greenberg, N.M. (2003) Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model. Prostate 55, 219–237.

    Article  PubMed  Google Scholar 

  15. Hurwitz, A.A., Foster, B.A., Kwong, E.D., Truong, T., Choi, E.M., Greenberg, N.M., Burg, M.B., and Allison, J.P. (2000) Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res. 60, 2444–2448.

    PubMed  CAS  Google Scholar 

  16. Giraldo, P. and Montoliu, L. (2001) Size matters: use of YACs, BACs and PACs in transgenic animals. Transgenic Res. 10, 83–103.

    Article  PubMed  CAS  Google Scholar 

  17. Schedl, A., Larin, Z., Montoliu, L., Thies, E., Kelsey, G., Lehrach, H., and Schutz, G. (1993) A method for the generation of YAC transgenic mice by pronuclear microinjection. Nucl. Acids Res. 21, 4783–4787.

    Article  PubMed  CAS  Google Scholar 

  18. Smith, D.J., Stevens, M.E., Sudanagunta, S.P., Bronson, R.T., Makhinson, M., Watabe, A.M., O’Dell, T.J., Fung, J., Weier, H.U., Cheng, J.F., and Rubin, E.M. (1997) Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome. Nat. Genet. 16, 28–36.

    Article  PubMed  CAS  Google Scholar 

  19. Wagner, E.F., Stewart, T.A., and Mintz, B. (1981) The human ß-globin gene and a functional viral thymidine kinase gene in developing mice. Proc. Natl. Acad. Sci. USA 78, 5016–5020.

    Article  PubMed  CAS  Google Scholar 

  20. Wilson, C., Bellen, H.J., and Gehring, W.J. (1990) Position effects on eukaryotic gene expression. Annu. Rev. Cell. Biol. 6, 679–714.

    Article  PubMed  CAS  Google Scholar 

  21. Palmiter, R.D. and Brinster, R.L. (1986) Germ-line transformation of mice. Annu. Rev. Genet. 20, 465–499.

    Article  PubMed  CAS  Google Scholar 

  22. Furth, P.A., Hennighausen, L., Baker, C., Beatty, B., and Woychick, R. (1991) The variability in activity of the universally expressed human cytomegalovirus immediate early gene 1 enhancer/promoter in transgenic mice. Nucl. Acids Res. 19, 6205–6208.

    Article  PubMed  CAS  Google Scholar 

  23. Lewis, P.F. and Emerman, M. (1994) Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J. Virol. 68, 510–516.

    PubMed  CAS  Google Scholar 

  24. Buchschacher, G.L. and Wong-Staal, F. (2000) Development of lentiviral vectors for gene therapy of human disease. Blood 95, 2499–2504.

    PubMed  CAS  Google Scholar 

  25. Miller, A.D. (1990) Retrovirus packaging cells. Hum. Gene Ther. 1, 5–14.

    Article  PubMed  CAS  Google Scholar 

  26. Zuffrey, R., Donello, J.E., Trono, D., and Hope, T.J. (1999) Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J. Virol. 73, 2886–2892.

    Google Scholar 

  27. Lois, C., Hong, E.J., Pease, S., Brown, E.J., and Baltimore, D. (2002) Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science 295, 868–872.

    Article  PubMed  CAS  Google Scholar 

  28. Imren, S., Farbry, M.E., Westerman, K.A., Pawliuk, R., Tang, P., Rosten, P.M., Nagel, R.L., Leboulch, P., Eaves, C.J., and Humphries, R.K. (2004) High level beta-globin expression and preferred intragenic integration after lentiviral transduction of human cord blood stem cells. J. Clin. Invest. 114, 953–962.

    PubMed  CAS  Google Scholar 

  29. Schroder, A.R., Shinn, P., Chen, H., Berry, C., Ecker, J.R., and Bushman, F. (2002) HIV-1 integration in the human genome favors active genes and local hotspots. Cell 110, 521–529.

    Article  PubMed  CAS  Google Scholar 

  30. Dann, C.T. (2007) New technology for an old favorite: lentiviral transgenesis and RNAi in rats. Transgenic Res. 16, 571–580.

    Article  PubMed  CAS  Google Scholar 

  31. Jahner, D., Stuhlmann, H., Stewart, C.L., Harbers, K., Lohler, J., Simon, I., and Jaenisch, R. (1982) De novo methylation and expression of retroviral genomes during mouse embryogenesis. Nature 298, 623–628.

    Article  PubMed  CAS  Google Scholar 

  32. Van den Brandt, J., Wang, D., Kwon, S.H., Heinkelein, M., and Reichardt, H.M. (2004) Lentivirally generated eGFP-transgenic rats allow efficient cell tracking in vivo. Genesis 39, 94–99.

    Article  PubMed  Google Scholar 

  33. Capecchi, M.R. (1989) Altering the genome by homologous recombination. Science 244, 1288–1292.

    Article  PubMed  CAS  Google Scholar 

  34. Evans, M.J. and Kaufman, M.H. (1981) Establishment in culture of pluripotent cells from mouse embryos. Nature 292, 154–156.

    Article  PubMed  CAS  Google Scholar 

  35. Martin, G.R. (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. USA 78, 7634–7636.

    Article  PubMed  CAS  Google Scholar 

  36. Abbondanzo, S.J., Gadi, I., and Stewart, C.L. (1993) Derivation of embryonic stem cell lines. Methods Enzymol. 225, 803–823.

    Article  PubMed  CAS  Google Scholar 

  37. Bradley, A., Evans, M., Kaufman, M.H., and Robertson, E. (1984) Formation of germ-line chimaeras from embryo derived teratocarcinoma cell lines. Nature 309, 255–256.

    Article  PubMed  CAS  Google Scholar 

  38. Doetschman, T., Gregg, R.G., Maeda, N., Hooper, M.L., Melton, D.W., Thompson, S., and Smithies, O. (1987) Targeted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature 330, 576–578.

    Article  PubMed  CAS  Google Scholar 

  39. Koentgen, F. and Stewart, C.L. (1993) Simple screening procedure to detect gene targeting events in embryonic stem cells. Methods Enzymol. 225, 878–890.

    Article  Google Scholar 

  40. Mansour, S., Thomas, K, and Capecchi, M.R. (1988) Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 336, 348–352.

    Article  PubMed  CAS  Google Scholar 

  41. Branda, C.S. and Dymecki, S.M. (2004) Talking about a revolution: the impact of site-specific recombinases on genetic analyses in mice. Dev. Cell 6, 7–28.

    Article  PubMed  CAS  Google Scholar 

  42. Sauer, B. and Henderson, N. (1989) Cre-stimulated recombination at loxP-containing DNA sequences placed into the mammalian genome. Nucl. Acids Res. 17, 147–161.

    Article  PubMed  CAS  Google Scholar 

  43. O’Gorman, S., Fox, D.T., and Wahl, G.M. (1991) Recombinase-mediated gene activation and site-specific integration in mammalian cells. Science 251, 1351–1355.

    Article  PubMed  Google Scholar 

  44. Lewandoski, M. (2001) Conditional control of gene expression in the mouse. Nat. Rev. Genet. 2, 743–755.

    Article  PubMed  CAS  Google Scholar 

  45. Forlino, A., Porter, F.D., Lee, E.J., Westphal, H., and Marini, J.C. (1999) Use of Cre/lox recombination system to develop a non-lethal knock-in murine model for osteogenesis imperfecta with an alpha1(I) G349C substitution. J. Biol. Chem. 274, 37923–37931.

    Article  PubMed  CAS  Google Scholar 

  46. Gu, H., Marth, J.D., Orban, P.C., Mossmann, H., and Rajewsky, K. (1994) Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science 265, 103–106.

    Article  PubMed  CAS  Google Scholar 

  47. Furuta, Y. and Behringer, R.R. (2005) Recent innovations in tissue-specific gene modifications in the mouse. Birth Defects Res 75, 43–57.

    Article  CAS  Google Scholar 

  48. Nagy, A. (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis 26, 99–109.

    Article  PubMed  CAS  Google Scholar 

  49. Feil, R., Brocard, J., Mascrez, B., LeMeur, M., Metzger, D., and Chambon, P. (1996) Ligand-activated site-specific recombination in mice. Proc. Natl. Acad. Sci. USA 93, 10887–10890.

    Article  PubMed  CAS  Google Scholar 

  50. Danielian, P.S., Muccino, D., Rowitch, D.H., Michael, S.K., and MacMahon, A.P. (1998) Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr. Biol. 8, 1323–1326.

    Article  PubMed  CAS  Google Scholar 

  51. Schwenk F., Kuehn R., Angrand, P.-O., Rajewsky K., and Stewart, A.F. (1998) Temporally and spatially regulated somatic mutagenesis in mice. Nucl. Acids Res. 26, 1427–1432.

    Article  PubMed  CAS  Google Scholar 

  52. Kellendonk, C., Tronche, F., Monaghan, A.P., Angrand, P.O., Stewart, F., and Schuetz, G. (1996) Regulation of Cre recombinase activity by the synthetic steroid RU486. Nucl. Acids Res. 24, 1404–1411.

    Article  PubMed  CAS  Google Scholar 

  53. Feil, R., Wagner, J., Metzger, D., and Chambon, P. (1997) Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains. Biochem. Biophys. Res. Commun. 237, 752–757.

    Article  PubMed  CAS  Google Scholar 

  54. Skvorak, K., Vissel, B., and Homanis, G.E. (2006) Production of conditional point mutant knockin mice. Genesis 44, 345–353.

    Article  PubMed  CAS  Google Scholar 

  55. Albert, H., Dale, E.C., Lee, E., and Ow, D.W. (1995) Site-specific integration of DNA into wild-type and mutant lox sites placed in the plant genome. Plant J. 7, 649–659.

    Article  PubMed  CAS  Google Scholar 

  56. Zhang, Z. and Lutz, B. (2002) Cre recombinase-mediated inversion using lox66 and lox71: method to introduce conditional point mutations into the CREB-binding protein. Nucl. Acids Res. 30, e90.

    Article  PubMed  Google Scholar 

  57. Schnuetgen, F., Doerflinger, N., Calleja, C., Wendling, O., Chambon, P., and Ghyselinck, N.B. (2003) A directional strategy for monitoring Cre-mediated recombination at the cellular level in the mouse. Nat. Biotechnol. 21, 562–565.

    Article  CAS  Google Scholar 

  58. Schnuetgen, F., De-Zolt, S., Van Sloun, P., Hollatz, M., Floss, T., Hansen, J., Altschmied, J., Seisenberger, C., Ghyselinck, N.B., Ruiz, P., Chambon, P., Wurst, W., and von Melchner, H. (2005) Genomewide production of multipurpose alleles for the functional analysis of the mouse genome. Proc. Natl. Acad. Sci. USA 102, 7221–7226.

    Article  CAS  Google Scholar 

  59. Bayascas, J.R., Sakamoto, K., Armit, L., Arthur, J.S.C., and Alessi, D.R. (2006) Evaluation of approaches to generation of tissue-specific knock-in mice. J. Biol. Chem. 281, 28772–28781.

    Article  PubMed  CAS  Google Scholar 

  60. Pelletier, J. and Sonnenberg, N. (1988) Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334, 320–325.

    Article  PubMed  CAS  Google Scholar 

  61. Jang, S.K., Krausslich, H.G., Nicklin, M.J., Duke, G.M., Palmenberg, A.C., and Wimmer, E. (1988) A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J. Virol. 62, 2636–2643.

    PubMed  CAS  Google Scholar 

  62. Bochov, Y.A. and Palmenberg, A.C. (2006) Translational efficiency of EMCV IRES in bicistronic vectors is dependent upon IRES sequence and gene location. BioTechniques 41, 283–292.

    Article  Google Scholar 

  63. Mizuguchi, H., Xu, Z., Ishii-Watabe, A., Uchida, E., and Hayakawa, T. (2000) IRES-dependent second gene expression is significantly lower than cap-dependent first gene expression in a bicistronic vector. Mol. Ther. 1, 376–382.

    Article  PubMed  CAS  Google Scholar 

  64. Okabe, M., Ikawa, M., Kominami, K., Nakanishi, T., and Nishimune, Y. (1997) Green mice as a source of ubiquitous green cells. FEBS Lett. 407, 313–319.

    Article  PubMed  CAS  Google Scholar 

  65. Hadjantonakis, A.K., Gertsenstein, M., Ikawa, M., Okabe, M., and Nagy, A. (1998) Generating green fluorescent mice by germline transmission of green fluorescent ES cells. Mech. Dev. 76, 79–90.

    Article  PubMed  CAS  Google Scholar 

  66. Shaner, N.C., Steinbach, P.A., and Tsien, R.Y. (2005) A guide to choosing fluorescent proteins. Nat. Methods 2, 905–909.

    Article  PubMed  CAS  Google Scholar 

  67. Hadjantonakis, A.K., Dickinson, M.E., Fraser, S.E., and Papaiannou, V.E. (2003) Technicolour transgenics: imaging tools for functional genomics in the mouse. Nat. Rev. Genet. 4, 613–625.

    Article  PubMed  CAS  Google Scholar 

  68. Livet, J., Weissmann, T.A., Kang, H., Draft, R.W., Lu, J., Bennis, R.A., Sanes, J.R., and Lichtman, J.W. (2007) Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450, 56–62.

    Article  PubMed  CAS  Google Scholar 

  69. Hopkin, M. (2006) Can super-antibody drugs be tamed? Nature 440, 855–856.

    CAS  Google Scholar 

  70. Lee, H., Zahra, D., Vogelzang, A., Newton, R., Thatcher, R., Quan, A., So, T., Zwirner, J., Koentgen, F., Padkjaer, S., Mackay, F., Whitfield, P.L., and Mackay, C.R. (2006) Human C5aR knock-in mice facilitate the production and assessment of anti-inflammatory monoclonal antibodies. Nat. Biotechnol. 24, 1279–1284.

    Article  PubMed  CAS  Google Scholar 

  71. Le, Y., Gagneten, S., Larson, T., Santha, E., Dobi, A., v. Agoston, D., and Sauer, B. (2003) Far-upstream elements are dispensable for tissue-specific proenkephalin expression using a Cre-mediated knock-in strategy. J. Neurochem. 84, 689–697.

    Google Scholar 

  72. Nyhan, W.L. (1997) The recognition of Lesch-Nyhan syndrome as an inborn error of purine metabolism. J. Inherit. Metab. Dis. 20, 171–178.

    Article  PubMed  CAS  Google Scholar 

  73. Williamson, D.J., Hooper, M.L., and Melton, D.W. (1992) Mouse models of hypoxanthine phosphoribosyltransferase deficiency. J. Inherit. Metab. Dis. 15, 665–673.

    Article  PubMed  CAS  Google Scholar 

  74. Oberdoerffer. P., Kanellopoulou, C., Heissmeyer, V., Paeper, C., Borowski, C., Aifantis, I., Rao, A., and Rajewsky, K. (2005) Efficiency of RNA interference in the mouse hematopoietic system varies between cell types and developmental stages. Mol. Cell. Biol. 25, 3896–3905.

    Article  PubMed  CAS  Google Scholar 

  75. Bronson, S.K., Plaehn, E.G., Kluckman, K.D., Hagaman, J.R., Maeda, N., and Smithies, O. (1996) Single-copy transgenic mice with chosen-site integration. Proc. Natl. Acad. Sci. USA 93, 9067–9072.

    Article  PubMed  CAS  Google Scholar 

  76. Hatada, S., Kuziel, W., Smithies, O., and Maeda, N. (1999) The influence of chromosomal location on the expression of two transgenes in mice. J. Biol. Chem. 274, 948–955.

    Article  PubMed  CAS  Google Scholar 

  77. Friedrich, G. and Soriano, P. (1991) Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. Genes Dev. 5, 1513–1523.

    Article  PubMed  CAS  Google Scholar 

  78. Zambrowicz, B.P., Imamoto, A., Fiering, S., Herzenberg, L.A., Kerr, W.G., and Soriano, P. (1997) Disruption of overlapping transcripts in the ROSA geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc. Natl. Acad. Sci. USA 94, 3789–3794.

    Article  PubMed  CAS  Google Scholar 

  79. Irion, S., Luche, H., Gadue, P., Fehling, H.J., Kennedy, M., and Keller, G. (2007) Identification and targeting of the ROSA26 locus in human embryonic stem cells. Nat. Biotech. 25, 1477–1482.

    Article  CAS  Google Scholar 

  80. Kisseberth, W.C., Brettingen, N.T., Lohse, J.K., and Sandgren, E.P. (1999) Ubiquitous expression of marker transgenes in mice and rats. Dev. Biol. 128–138.

    Google Scholar 

  81. Strathdee, D., Ibbotson, H., and Grant, S.G.N. (2006) Expression of transgenes targeted to the Gt(ROSA)26Sor locus is orientation dependent. PloS ONE 1, e4.

    Article  PubMed  Google Scholar 

  82. Lai, K.M.V., Gonzalez, M., Poueymirou, W.T., Kline, W.O., Na, E., Zlotchenko, E., Stitt, T.N., Economides, A.N., Yancopoulos, G.D., and Glass, D.J. (2004) Conditional activation of Akt in adult skeletal muscle induces rapid hypertrophy. Mol. Cell. Biol. 24, 9295–9304.

    Article  PubMed  CAS  Google Scholar 

  83. Lakso, M., Sauer, B., Mosinger, B., Lee, E.J., Manning, R.W., Yu, S.H., Mulder, K.L., and Westphal, H. (1992). Targeted oncogene activation by site-specific recombination in transgenic mice. Proc. Natl. Acad. Sci. USA 89, 6232–6236.

    Article  PubMed  CAS  Google Scholar 

  84. Jackson, E.L., Willis, N., Mercer, K., Bronson, R.T., Crowley, D., Montoya, R., Jacks, T., and Tuveson, D.A. (2001) Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 15, 3243–3248.

    Article  PubMed  CAS  Google Scholar 

  85. Fire, A., Xu, S., Montgomery, M.K., Kostas, S.S., Driver, S.E., and Mello, C.C. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806–811.

    Article  PubMed  CAS  Google Scholar 

  86. McManus, M.T. and Sharp, P.A. (2002) Gene silencing in mammals by small interfering RNAs. Nat. Rev. Genet. 3, 737–747.

    Article  PubMed  CAS  Google Scholar 

  87. Hannon, G.J. (2002) RNA interference. Nature 418, 244–251.

    Article  PubMed  CAS  Google Scholar 

  88. Novina, C.D. and Sharp, P.A. (2004) The RNAi revolution. Nature 430, 161–164.

    Article  PubMed  CAS  Google Scholar 

  89. Ui-Tei, K., Naito, Y., Takahashi, F., Haraguchi, T., Ohki-Hamazaki, H., Juni, A., Ueda, R., and Saigo, K. (2004) Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucl. Acids Res. 32, 936–948.

    Article  PubMed  CAS  Google Scholar 

  90. Meister, G. and Tuschl, T. (2004) Mechanisms of gene silencing by double-stranded RNA. Nature 431, 343–349.

    Article  PubMed  CAS  Google Scholar 

  91. Hasuwa, H., Kaseda, K., Einarsdottir, T., and Okabe, M. (2002) Small interfering RNA and gene silencing in transgenic mice and rats. FEBS Lett. 532, 227–230.

    Article  PubMed  CAS  Google Scholar 

  92. Mitani, T. and Yokota, T. (2005) RNA interference as a tool for producing knockdown mice. J. Mamm. Ova Res. 22, 139–151.

    Article  Google Scholar 

  93. Hou, J., Schan, Q., Wang, T., Gomes, A.S., Yan, Q.S., Paul, D.L., Bleich, M., and Goodenough, D.A. (2007) Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. J. Biol. Chem. 282, 17114–17122.

    Article  PubMed  CAS  Google Scholar 

  94. Lu, W., Yamamoto, V., Ortega, B., and Baltimore, D. (2004) Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. Cell 119, 97–108.

    Article  PubMed  CAS  Google Scholar 

  95. Kissler, S., Stern, P., Takahashi, K., Hunter, K., Peterson, L.B., and Wicker, L.S. (2006) In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to type 1 diabetes. Nat. Genet. 38, 479–483.

    Article  PubMed  CAS  Google Scholar 

  96. Grimm D., Streetz, K.L., Jopling, C.L., Storm, T.A., Pandey, K., Davis, C.R., Marion, P., Salzar, F., and Kay, M.A. (2006). Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441, 537–541.

    Article  PubMed  CAS  Google Scholar 

  97. Amar, L., Desclaux, M., Faucon-Biguet, N., Mallet, J., and Vogel, R. (2006) Control of small inhibitory RNA levels and RNA interference by doxycycline induced activation of a minimal RNA polymerase III promoter. Nucl. Acids Res. 34, e37.

    Article  PubMed  Google Scholar 

  98. Szulc, J., Wiznerowicz, M., Sauvain, M.-O., Trono, D., and Aebischer, P. (2006). A versatile tool for conditional gene expression and knockdown. Nat. Methods 3, 109–116.

    Article  PubMed  CAS  Google Scholar 

  99. Moosmann, P. Georgiev, O., Thiesen, H.J., Hagmann, M., and Schaffner, W. (1997) Silencing of RNA polymerases II and III-dependent transcription by the KRAB protein domain of KOX1, a Kruppel-type zinc finger factor. Biol. Chem. 378, 669–677.

    Article  PubMed  CAS  Google Scholar 

  100. Fritsch, L., Martinez, L.A., Sekhri, R., Naguibneva, I., Gerard, M., Vandromme, M., Schaeffer, L., and Harel-Bellan, A. (2004) Conditional gene knock-down by Cre-dependent short interfering RNAs. EMBO Rep. 5, 178–182.

    Article  PubMed  CAS  Google Scholar 

  101. Hitz, C., Wurst, W., and Kuhn, R. (2007) Conditional brain-specific knockdown of MAPK using Cre/loxP regulated RNA interference. Nucl. Acids Res. 35, e90.

    Article  PubMed  Google Scholar 

  102. Steuber-Buchberger, P., Wurst, W., and Kuhn, R. (2008) Simultaneous cre-mediated conditional knockdown of two genes in mice. Genesis 46, 144–151.

    Article  PubMed  CAS  Google Scholar 

  103. Tiscornia, G., Tergaonkar, V., Galimi, F., and Verma, I.M. (2004) Cre recombinase-inducible RNA interference mediated by lentiviral vectors. Proc. Natl. Acad. Sci. USA 101, 7347–7351.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Drs. David Tarlinton and Louise McKenzie for critical reading of the manuscript, and Ozgene scientific staff for fruitful discussions.

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Authors and Affiliations

  1. Ozgene Pty. Ltd., Bentley DC, Western Australia, Australia

    Frank Koentgen, Gabriele Suess & Dieter Naf

Authors
  1. Frank Koentgen
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  2. Gabriele Suess
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  3. Dieter Naf
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Editors and Affiliations

  1. The Jackson Laboratory, Main Street 600, Bar Harbor, 04609, Maine, USA

    Gabriele Proetzel

  2. Jackson Laboratory, Main Street 600, Bar Harbor, 04609, USA

    Michael V. Wiles

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Koentgen, F., Suess, G., Naf, D. (2010). Engineering the Mouse Genome to Model Human Disease for Drug Discovery. In: Proetzel, G., Wiles, M. (eds) Mouse Models for Drug Discovery. Methods in Molecular Biology, vol 602. Humana Press. https://doi.org/10.1007/978-1-60761-058-8_4

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  • DOI: https://doi.org/10.1007/978-1-60761-058-8_4

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60761-057-1

  • Online ISBN: 978-1-60761-058-8

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