Abstract
In the past 2 years, new gene-targeting approaches using adeno-associated virus and designer zinc-finger nucleases have been successfully applied to the production of genetically modified ferrets, pigs, mice and zebrafish. Gene targeting using these tools has been combined with somatic cell nuclear transfer and germ cell transplantation to generate gene-targeted animal models. These new technical advances, which do not require the generation of embryonic stem cell-derived chimeras, will greatly accelerate the production of non-mouse animal models for biomedical research.
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References
Rogers CS, Abraham WM, Brogden KA, Engelhardt JF, Fisher JT, McCray Jr PB et al. The porcine lung as a potential model for cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 2008; 295: L240–L263.
Liu X, Luo M, Zhang L, Ding W, Yan Z, Engelhardt JF . Bioelectric properties of chloride channels in human, pig, ferret, and mouse airway epithelia. Am J Respir Cell Mol Biol 2007; 36: 313–323.
Rogers CS, Hao Y, Rokhlina T, Samuel M, Stoltz DA, Li Y et al. Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. J Clin Invest 2008; 118: 1571–1577.
Rogers CS, Stoltz DA, Meyerholz DK, Ostedgaard LS, Rokhlina T, Taft PJ et al. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 2008; 321: 1837–1841.
Sun X, Yan Z, Yi Y, Li Z, Lei D, Rogers CS et al. Adeno-associated virus-targeted disruption of the CFTR gene in cloned ferrets. J Clin Invest 2008; 118: 1578–1583.
Fujimura T, Murakami H, Kurome M, Takahagi Y, Shigehisa T, Nagashima H . Effects of recloning on the efficiency of production of alpha 1,3-galactosyltransferase knockout pigs. J Reprod Dev 2008; 54: 58–62.
Dobrinski I . Transplantation of germ line stem cells for the study and manipulation of spermatogenesis. Ernst Schering Res Found Workshop 2006; 60: 175–193.
Dobrinski I . Male germ cell transplantation. Reprod Domest Anim 2008; 43 (Suppl 2): 288–294.
Kanatsu-Shinohara M, Inoue K, Lee J, Miki H, Ogonuki N, Toyokuni S et al. Anchorage-independent growth of mouse male germline stem cells in vitro. Biol Reprod 2006; 74: 522–529.
Kanatsu-Shinohara M, Inoue K, Ogonuki N, Miki H, Yoshida S, Toyokuni S et al. Leukemia inhibitory factor enhances formation of germ cell colonies in neonatal mouse testis culture. Biol Reprod 2007; 76: 55–62.
Kubota H, Brinster RL . Technology insight: in vitro culture of spermatogonial stem cells and their potential therapeutic uses. Nat Clin Pract Endocrinol Metab 2006; 2: 99–108.
Kanatsu-Shinohara M, Ikawa M, Takehashi M, Ogonuki N, Miki H, Inoue K et al. Production of knockout mice by random or targeted mutagenesis in spermatogonial stem cells. Proc Natl Acad Sci USA 2006; 103: 8018–8023.
Ryu BY, Orwig KE, Oatley JM, Lin CC, Chang LJ, Avarbock MR et al. Efficient generation of transgenic rats through the male germline using lentiviral transduction and transplantation of spermatogonial stem cells. J Androl 2007; 28: 353–360.
Honaramooz A, Megee S, Zeng W, Destrempes MM, Overton SA, Luo J et al. Adeno-associated virus (AAV)-mediated transduction of male germ line stem cells results in transgene transmission after germ cell transplantation. FASEB J 2008; 22: 374–382.
Lieschke GJ, Currie PD . Animal models of human disease: zebrafish swim into view. Nat Rev Genet 2007; 8: 353–367.
Skromne I, Prince VE . Current perspectives in zebrafish reverse genetics: moving forward. Dev Dyn 2008; 237: 861–882.
Jao LE, Maddison L, Chen W, Burgess SM . Using retroviruses as a mutagenesis tool to explore the zebrafish genome. Brief Funct Genomic Proteomic 2008; 7: 427–443.
Fan L, Collodi P . Zebrafish embryonic stem cells. Methods Enzymol 2006; 418: 64–77.
Fan L, Moon J, Crodian J, Collodi P . Homologous recombination in zebrafish ES cells. Transgenic Res 2006; 15: 21–30.
Woods IG, Schier AF . Targeted mutagenesis in zebrafish. Nat Biotechnol 2008; 26: 650–651.
Cathomen T, Joung JK . Zinc-finger nucleases: the next generation emerges. Mol Ther 2008; 16: 1200–1207.
Fu F, Sander JD, Maeder M, Thibodeau-Beganny S, Joung JK, Dobbs D et al. Zinc Finger Database (ZiFDB): a repository for information on C2H2 zinc fingers and engineered zinc-finger arrays. Nucleic Acids Res 2009; 37: D279–D283.
Porteus M . Design and testing of zinc finger nucleases for use in mammalian cells. Methods Mol Biol 2008; 435: 47–61.
Doyon Y, McCammon JM, Miller JC, Faraji F, Ngo C, Katibah GE et al. Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 2008; 26: 702–708.
Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA . Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol 2008; 26: 695–701.
Santiago Y, Chan E, Liu PQ, Orlando S, Zhang L, Urnov FD et al. Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases. Proc Natl Acad Sci USA 2008; 105: 5809–5814.
Moehle EA, Rock JM, Lee YL, Jouvenot Y, DeKelver RC, Gregory PD et al. Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases. Proc Natl Acad Sci USA 2007; 104: 3055–3060.
Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA, Liu O et al. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol 2008; 26: 808–816.
Lombardo A, Genovese P, Beausejour CM, Colleoni S, Lee YL, Kim KA et al. Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat Biotechnol 2007; 25: 1298–1306.
Takehashi M, Kanatsu-Shinohara M, Miki H, Lee J, Kazuki Y, Inoue K et al. Production of knockout mice by gene targeting in multipotent germline stem cells. Dev Biol 2007; 312: 344–352.
Conrad S, Renninger M, Hennenlotter J, Wiesner T, Just L, Bonin M et al. Generation of pluripotent stem cells from adult human testis. Nature 2008; 465: 344–349.
Yang SH, Cheng PH, Banta H, Piotrowska-Nitsche K, Yang JJ, Cheng EC et al. Towards a transgenic model of Huntington's disease in a non-human primate. Nature 2008; 453: 921–924.
Byrne JA, Pedersen DA, Clepper LL, Nelson M, Sanger WG, Gokhale S et al. Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature 2007; 450: 497–502.
Cram DS, Song B, Trounson AO . Genotyping of Rhesus SCNT pluripotent stem cell lines. Nature 2007; 450: E12–E14.
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Yan, Z., Sun, X. & Engelhardt, J. Progress and prospects: techniques for site-directed mutagenesis in animal models. Gene Ther 16, 581–588 (2009). https://doi.org/10.1038/gt.2009.16
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DOI: https://doi.org/10.1038/gt.2009.16
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