Skip to main content
SpringerLink
Log in

Animal transgenesis: state of the art and applications

  • Review Article
  • Published:
Journal of Applied Genetics Aims and scope Submit manuscript

Abstract

There is a constant expectation for fast improvement of livestock production and human health care products. The advent of DNA recombinant technology and the possibility of gene transfer between organisms of distinct species, or even distinct phylogenic kingdoms, has opened a wide range of possibilities. Nowadays we can produce human insulin in bacteria or human coagulation factors in cattle milk. The recent advances in gene transfer, animal cloning, and assisted reproductive techniques have partly fulfilled the expectation in the field of livestock transgenesis. This paper reviews the recent advances and applications of transgenesis in livestock and their derivative products. At first, the state of art and the techniques that enhance the efficiency of livestock transgenesis are presented. The consequent reduction in the cost and time necessary to reach a final product has enabled the multiplication of transgenic prototypes around the world. We also analyze here some emerging applications of livestock transgenesis in the field of pharmacology, meat and dairy industry, xenotransplantation, and human disease modeling. Finally, some bioethical and commercial concerns raised by the transgenesis applications are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Auchincloss H, Jr., Sachs DH, 1998. Xenogeneic transplantation. Annu Rev Immunol 16: 433–470.

    Article  CAS  PubMed  Google Scholar 

  • Barthel R, Feng J, Piedrahita JA, McMurray DN, Templeton JW, Adams LG, 2001. Stable transfection of the bovine NRAMP1 gene into murine RAW264.7 cells: effect onBrucella abortus survival. Infect Immun 69: 3110–3119.

    Article  CAS  PubMed  Google Scholar 

  • Betts D, Bordignon V, Hill J, Winger Q, Westhusin M, Smith L, King W, 2001. Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle. Proc Natl Acad Sci USA 98: 1077–1082.

    Article  CAS  PubMed  Google Scholar 

  • Bleck GT, White BR, Miller DJ, Wheeler MB, 1998. Production of bovine alpha-lactalbumin in the milk of transgenic pigs. J Anim Sci 76: 3072–3078.

    CAS  PubMed  Google Scholar 

  • Brackett BG, Baranska W, Sawicki W, Koprowski H, 1971. Uptake of heterologous genome by mammalian spermatozoa and its transfer to ova through fertilization. Proc Natl Acad Sci USA 68: 353–357.

    Article  CAS  PubMed  Google Scholar 

  • Brophy B, Smolenski G, Wheeler T, Wells D, L’Huillier P, Laible G, 2003. Cloned transgenic cattle produce milk with higher levels of beta-casein and kappa-casein. Nat Biotechnol 21: 157–162.

    Article  CAS  PubMed  Google Scholar 

  • Bueler H, Aguzzi A, Sailer A, Greiner RA, Autenried P, Aguet M, Weissmann C, 1993. Mice devoid of PrP are resistant to scrapie. Cell 73: 1339–1347.

    Article  CAS  PubMed  Google Scholar 

  • Bueler H, Fischer M, Lang Y, Bluethmann H, Lipp HP, DeArmond SJ, et al. 1992. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356: 577–582.

    Article  CAS  PubMed  Google Scholar 

  • Campbell KH, Mc Whir J, Ritchie WA, Wilmut I, 1996. Sheep cloned by nuclear transfer from a cultured cell line. Nature 380: 64–66.

    Article  CAS  PubMed  Google Scholar 

  • Capecchi MR, 1989. Altering the genome by homologous recombination. Science 244: 1288–1292.

    Article  CAS  PubMed  Google Scholar 

  • Caplen NJ, Kinrade E, Sorgi F, Gao X, Gruenert D, Geddes D, et al. 1995. In vitro liposome-mediated DNA transfection of epithelial cell lines using the cationic liposome DC-Chol/DOPE. Gene Ther 2: 603–613.

    CAS  PubMed  Google Scholar 

  • Cawthon RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA, 2003. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361: 393–395.

    Article  CAS  PubMed  Google Scholar 

  • Celebi C, Guillaudeux T, Auvray P, Vallet-Erdtmann V, Jegou B, 2003. The Making of “Transgenic Spermatozoa”. Biol Reprod 68: 1477–1483.

    Article  CAS  PubMed  Google Scholar 

  • Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, et al. 1998. Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280: 1256–1258.

    Article  CAS  PubMed  Google Scholar 

  • Chan AW, Homan EJ, Ballou LU, Burns JC, Bremel RD, 1998. Transgenic cattle produced by reverse-transcribed gene transfer in oocytes. Proc Natl Acad Sci USA 95: 14028–14033.

    Article  CAS  PubMed  Google Scholar 

  • Chen CA, Okayama H, 1988. Calcium phosphate-mediated gene transfer: a highly efficient transfection system for stably transforming cells with plasmid DNA. Biotechniques 6: 632–638.

    CAS  PubMed  Google Scholar 

  • Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, et al. 1998. Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280: 1256–1258.

    Article  CAS  PubMed  Google Scholar 

  • Clark AJ, Bissinger P, Bullock DW, Damak S, Wallace R, Whitelaw CB, Yull F, 1994. Chromosomal position effects and the modulation of transgene expression. Reprod Fertil Dev 6: 589–598.

    Article  CAS  PubMed  Google Scholar 

  • Clark J, Whitelaw B, 2003. A future fortransgenic livestock. Nat Rev Genet 4: 825–833.

    Article  CAS  PubMed  Google Scholar 

  • Cohen SN, Chang AC, Boyer HW, Helling RB, 1973. Construction of biologically functional bacterial plasmids in vitro. Proc Natl Acad Sci USA 70: 3240–3244.

    Article  CAS  PubMed  Google Scholar 

  • Denman J, Hayes M, O’Day C, Edmunds T, Bartlett C, Hirani S, et al. 1991. Transgenic expression of a variant of human tissue-type plasminogen activator in goat milk: purification and characterization of the recombinant enzyme. Biotechnology (NY) 9: 839–843.

    Article  CAS  Google Scholar 

  • Denning C, Burl S, Ainslie A, Bracken J, Dinnyes A, Fletcher J, et al. 2001. Deletion of the alpha (1, 3) galactosyl transferase (GGTA1) gene and the prion protein (PrP) gene in sheep. Nat Biotechnol 19: 559–562.

    Article  CAS  PubMed  Google Scholar 

  • Detwiler LA, Rubenstein R, 2000. Bovine spongiform encephalopathy: an overview. Asaio J 46: S73–79.

    Article  CAS  PubMed  Google Scholar 

  • Diamond LE, Quinn CM, Martin MJ, Lawson J, Platt JL, Logan JS, 2001. A human CD46 transgenic pig model system for the study of discordant xenotransplantation. Transplantation 71: 132–142.

    Article  CAS  PubMed  Google Scholar 

  • Djojosubroto MW, Choi YS, Lee HW, Rudolph KL, 2003. Telomeres and telomerase in aging, regeneration and cancer. Mol Cells 15: 164–175.

    CAS  PubMed  Google Scholar 

  • Draghia-Akli R, Fiorotto ML, Hill LA, Malone PB, Deaver DR, Schwartz RJ, 1999. Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs. Nat Biotechnol 17: 1179–1183.

    Article  CAS  PubMed  Google Scholar 

  • Dyck MK, Lacroix D, Pothier F, Sirard MA, 2003. Making recombinant proteins in animals — different systems, different applications. Trends Biotechnol 21: 394–399.

    Article  CAS  PubMed  Google Scholar 

  • Ebert KM, Selgrath JP, DiTullio P, Denman J, Smith TE, Memon MA, et al. 1991. Transgenic production of a variant of human tissue-type plasminogen activator in goat milk: generation of transgenic goats and analysis of expression. Biotechnology (NY) 9: 835–838.

    Article  CAS  Google Scholar 

  • Ebert KM, DiTullio P, Barry CA, Schindler JE, Ayres SL, Smith TE, et al. 1994. Induction of human tissue plasminogen activator in the mammary gland of transgenic goats. Biotechnology (NY) 12: 699–702.

    Article  CAS  Google Scholar 

  • Evans MJ, Kaufman MH, 1981. Establishment in culture of pluripotential cells from mouse embryos. Nature 292: 154–156.

    Article  CAS  PubMed  Google Scholar 

  • Fodor WL, Williams BL, Matis LA, Madri JA, Rollins SA, Knight JW, et al. 1994. Expression of a functional human complement inhibitor in a transgenic pig as a model for the prevention of xenogeneic hyperacute organ rejection. Proc Natl Acad Sci USA 91: 11153–11157.

    Article  CAS  PubMed  Google Scholar 

  • Gibbons J, Arat S, Rzucidlo J, Miyoshi K, Waltenburg R, Respess D, et al. 2002. Enhanced survivability of cloned calves derived from roscovitine-treated adult somatic cells. Biol Reprod 66: 895–900.

    Article  CAS  PubMed  Google Scholar 

  • Golovan SP, Meidinger RG, Ajakaiye A, Cottrill M, Wiederkehr MZ, Barney DJ, et al. 2001. Pigs expressing salivary phytase produce low-phosphorus manure. Nat Biotechnol 19: 741–745.

    Article  CAS  PubMed  Google Scholar 

  • Gordon JW, Ruddle FH, 1981. Integration and stable germ line transmission of genes injected into mouse pronuclei. Science 214: 1244–1246.

    Article  CAS  PubMed  Google Scholar 

  • Grobet L, Martin LJ, Poncelet D, Pirottin D, Brouwers B, Riquet J, et al. 1997. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet 17: 71–74.

    Article  CAS  PubMed  Google Scholar 

  • Hammer RE, Pursel VG, Rexroad CE, Jr., Wall RJ, Bolt DJ, Ebert KM, et al. 1985. Production of transgenic rabbits, sheep and pigs by microinjection. Nature 315: 680–683.

    Article  CAS  PubMed  Google Scholar 

  • Hanrahan JP, Gregan SM, Mulsant P, Mullen M, Davis GH, Powell R, Galloway SM, 2004. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheeo (Ovis aries). Biol Reprod 70: 900–909.

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa K, Motsuchi W, Tanaka S, Dosako S, 1994. Inhibition with lactoferrin of in nitro infection with human herpes virus. Jpn J Med Sci Biol 47: 73–85.

    CAS  PubMed  Google Scholar 

  • Honaramooz A, Behboodi E, Blash S, Megee SO, Dobrinski I, 2003. Germ cell transplantation in goats. Mol Reprod Dev 64: 422–428.

    Article  CAS  PubMed  Google Scholar 

  • Honaramooz A, Megee SO, Dobrinski I, 2002. Germ cell transplantation in pigs. Biol Reprod 66: 21–28.

    Article  CAS  PubMed  Google Scholar 

  • Human Genome Sequencing C, 2004. Finishing the euchromatic sequence of the human genome. Nature 431: 931–945.

    Article  CAS  Google Scholar 

  • Iguma LT, Lisauskas SF, Melo EO, Franco MM, Pivato I, Vianna GR, et al. 2005. Development of bovine embryos reconstructed by nuclear transfer of transfected and non-transfected adult fibroblast cells. Genet Mol Res 4: 55–66.

    PubMed  Google Scholar 

  • Imaizumi T, Lankford KL, Burton WV, Fodor WL, Kocsis JD, 2000. Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord. Nat Biotechnol 18: 949–953.

    Article  CAS  PubMed  Google Scholar 

  • Jackson DA, Symons RH, Berg P, 1972. Biochemical method for inserting new genetic information into DNA of Simian Virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proc Natl Acad Sci USA 69: 2904–2909.

    Article  CAS  PubMed  Google Scholar 

  • Jaenisch R, Fan H, Croker B, 1975. Infection of preimplantation mouse embryos and of newborn mice with leukemia virus: tissue distribution of viral DNA and RNA and leukemogenesis in the adult animal. Proc Natl Acad Sci USA 72: 4008–4012.

    Article  CAS  PubMed  Google Scholar 

  • Jost B, Vilotte JL, Duluc I, Rodeau JL, Freund JN, 1999. Production of low-lactose milk by ectopic expression of intestinal lactase in the mouse mammary gland. Nat Biotechnol 17: 160–164.

    Article  CAS  PubMed  Google Scholar 

  • Juengel JL, Hudson NL, Heath DA, Smith P, Reader KL, Lawrence SB, et al. 2002. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep. Biol Reprod 67: 1777–1789.

    Article  CAS  PubMed  Google Scholar 

  • Kang Y, Jimenez-Flores R, Richardson T, 1986. Casein genes and genetic engineering of the caseins. Basic Life Sci 37: 95–111.

    CAS  PubMed  Google Scholar 

  • Karatzas CN, 2003. Designer milk from transgenic clones. Nat Biotechnol 21: 138–139.

    Article  CAS  PubMed  Google Scholar 

  • Karatzas CN, Turner JD, 1997. Toward altering milk composition by genetic manipulation: current status and challenges. J Dairy Sci 80: 2225–2232.

    Article  CAS  PubMed  Google Scholar 

  • Kasinathan P, Knott JG, Moreira PN, Burnside AS, Jerry DJ, Robl JM, 2001a. Effect of fibroblast donor cell age and cell cycle on development of bovine nuclear transfer embryos in vitro. Biol Reprod 64: 1487–1493.

    Article  CAS  PubMed  Google Scholar 

  • Kasinathan P, Knott JG, Wang Z, Jerry DJ, Robl JM, 2001b. Production of calves from G1 fibroblasts. Nat Biotechnol 19: 1176–1178.

    Article  CAS  PubMed  Google Scholar 

  • Keefer CL, 2004. Production of bioproducts through the use of transgenic animal models. Anim Reprod Sci 82-83: 5–12.

    Article  CAS  PubMed  Google Scholar 

  • Kerr DE, Plaut K, Branley AJ, Williamson CM, Lax AJ, Moore K, et al. 2001. Lysostaphin expression in mammary glands confers protection against staphylococcal infection in transgenic mice. Nat Biotechnol 19: 66–70.

    Article  CAS  PubMed  Google Scholar 

  • Kerr DE, Wellnitz O, 2003. Mammary expression of new genes to combat mastitis. J Anim Sci 81: 38–47.

    CAS  PubMed  Google Scholar 

  • Kovesdi I, Brough DE, Bruder JT, Wickham TJ, 1997. Adenoviral vectors for gene transfer. Curr Opin Biotechnol 8: 583–589.

    Article  CAS  PubMed  Google Scholar 

  • Krimpenfort P, Rademakers A, Eyestone W, van der Schans A, van den Broek S, Kooiman P, et al. 1991. Generation of transgenic dairy cattle using ‘in vitro’ embryo production. Biotechnology (NY) 9: 844–847.

    Article  CAS  Google Scholar 

  • Kues WA, Niemann H, 2004. The contribution of farm animals to human health. Trends Biotechnol 22: 286–294.

    Article  CAS  PubMed  Google Scholar 

  • Kuroiwa Y, Kasinathan P, Choi YJ, Naeem R, Tomizuka K, Sullivan EJ, et al. 2002. Cloned transchromosomic calves producing human immunoglobulin. Nat Biotechnol 20: 889–894.

    Article  CAS  PubMed  Google Scholar 

  • Kuroiwa Y, Kasinathan P, Matsushita H, Sathiyaselan J, Sullivan EJ, Kakitani M, et al. 2004. Sequential targeting of the genes encoding immunoglobulin-mu and prion protein in cattle. Nat Genet 36: 775–780.

    Article  CAS  PubMed  Google Scholar 

  • Lanza RP, Cibelli JB, Blackwell C, Cristofalo VJ, Francis MK, Baerlocher GM, et al. 2000. Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science 288: 665–669.

    Article  CAS  PubMed  Google Scholar 

  • Lazaris A, Arcidiacono S, Huang Y, Zhou JF, Duguay F, Chretien N, et al. 2002. Spider silk fibers spun from soluble recombinant silk produced in mammalian cells. Science 295: 472–476.

    Article  CAS  PubMed  Google Scholar 

  • Li L, Shen W, Min L, Dong H, Sun Y, Pan Q, 2006. Human lactoferrin transgenic rabbits produced efficiently using dimethylsulfoxide-sperm-mediated gene transfer. Reprod Fertil Dev 18: 689–695.

    Article  CAS  PubMed  Google Scholar 

  • Lipinski D, Jura J, Kalak R, Plawski A, Kala M, Szalata M, et al. 2003. Transgenic rabbit producing human growth hormone in milk. J Appl Genet 44: 165–174.

    PubMed  Google Scholar 

  • Maione B, Lavitrano M, Spadafora C, Kiessling AA, 1998. Sperm-mediated gene transfer in mice. Mol Reprod Dev 50: 406–409.

    Article  CAS  PubMed  Google Scholar 

  • Martin GR, 1981. Isolation of a pluripotent cell line from early mouse embryos cultured in medium condiyioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78: 7634–7638.

    Article  CAS  PubMed  Google Scholar 

  • Marx J, 2003. Medicine. Building better mouse models for studying cancer. Science 299: 1972–1975.

    Article  CAS  PubMed  Google Scholar 

  • Massoud M, Attal J, Thepot D, Pointu H, Stinnakre MG, Theron MC, et al. 1996. The deleterious effects of human erythropoietin gene driven by the rabbit whey acidic protein gene promoter in transgenic rabbits. Reprod Nutr Dev 36: 555–563.

    Article  CAS  PubMed  Google Scholar 

  • McCreath KJ, Howcroft J, Campbell KH, Colman A, Schnieke AE, Kind AJ, 2000. Production of gene-targeted sheep by nuclear transfer from cultured somatic cells. Nature 405: 1066–1069.

    Article  CAS  PubMed  Google Scholar 

  • McKee C, Gibson A, Dalrymple M, Emslie L, Garner I, Cottingham I, 1998. Production of biologically active salmon calcitonin in the milk of transgenic rabbits. Nat Biotechnol 16: 647–651.

    Article  CAS  PubMed  Google Scholar 

  • McPherron AC, Lawler AM, Lee SJ, 1997. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387: 83–90.

    Article  CAS  PubMed  Google Scholar 

  • McPherron AC, Lee SJ, 1997. Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci USA 94: 12457–12461.

    Article  CAS  PubMed  Google Scholar 

  • Melo EO, Sousa RV, Iguma LT, Franco MM, Rech EL, Rumpf R, 2005. Isolation of transfected fibroblast clones for use in nuclear transfer and transgene detection in cattle embryos. Genet Mol Res 4: 812–821.

    CAS  PubMed  Google Scholar 

  • Michalak E, Lipinski D, Slomski R, 2006. Loop formation by the transgene WAP: 6 × HishGH in transgenic rabbit fibroblast, revealed by fluorescence in situ hybridization to nuclear halos. J Appl Genet 47: 247–249.

    Article  PubMed  Google Scholar 

  • Miller HI, 2002. As biotech turns 20. Nat Rev Drug Discov 1: 1007–1008.

    Article  CAS  PubMed  Google Scholar 

  • Mogford JE, Liu WR, Reid R, Chiu CP, Said H, Chen SJ, et al. 2006. Adenoviral human telomerase reverse transcriptase dramatically improves ischemic wound healing without detrimental immune response in an aged rabit model. Hum Gene Ther 17: 651–660.

    Article  CAS  PubMed  Google Scholar 

  • Muller M, Brenig B, Winnacker EL, Brem G, 1992. Transgenic pigs carrying cDNA copies encoding the murine Mx1 protein which confers resistance to influenza virus infection. Gene 121: 263–270.

    Article  CAS  PubMed  Google Scholar 

  • Nagano M, Brinster CJ, Orwig KE, Ryu BY, Avarbock MR, Brinster RL, 2001. Transgenic mice produced by retroviral transduction of male germ-line stem cells. Proc Natl Acad Sci USA 98: 13090–13095.

    Article  CAS  PubMed  Google Scholar 

  • Nibbering PH, Ravensbergen E, Welling MM, van Berkel LA, van Berkel PH, Pauwels EK, Nuijens JH, 2001. Human lactoferrin and peptides derived from its N terminus are highly effective against infections with antibiotic-resistant bacteria. Infect Immun 69: 1469–1476.

    Article  CAS  PubMed  Google Scholar 

  • Niemann H, Halter R, Carnwath JW, Herrmann D, Lemme E, Paul D, 1999. Expression of human blood clotting factor VIII in the mammary gland of transgenic sheep. Transgenic Res 8: 237–247.

    Article  CAS  PubMed  Google Scholar 

  • Noble MS, Rodriguez-Zas S, Cook JB, Bleck GT, Hurley WL, Wheeler MB, 2002. Lactational performance of first-parity transgenic gilts expressing bovine alpha-lactalbumin in their milk. J Anim Sci 80; 1090–1096.

    CAS  PubMed  Google Scholar 

  • Nottle MB, Haskard KA, Verma PJ, Du ZT, Grupen CG, McIlfatrick SM, et al. 2001. Effect of DNA concentration on transgenesis rates in mice and pigs. Transgenic Res 10: 523–531.

    Article  CAS  PubMed  Google Scholar 

  • Nuijens JH, van Berkel PH, Geerts ME, Hartevelt PP, de Boer HA, van Veen HA, Pieper FR, 1997. Characterization of recombinant human lactoferrin secreted in milk of transgenic mice. J Biol Chem 272: 8802–8807.

    Article  CAS  PubMed  Google Scholar 

  • Oliveira RR, Carvalho DM, Lisauskas S, Mello E, Vianna GR, Dode MA, et al. 2005. Effectiveness of liposomes to transfect livestock fibroblasts. Genet Mol Res 4: 185–196.

    CAS  PubMed  Google Scholar 

  • Paleyanda RK, Velander WH, Lee TK, Scandella DH, Gwazdauskas FC, Knight JW, 1997. Transgenic pigs produce functional human factor VIII in milk. Nat Biotechnol 15: 971–975.

    Article  CAS  PubMed  Google Scholar 

  • Palmiter RD, Brinster RL, Hammer RE, Trumbauer ME, Rosenfeld MG, Birnberg NC, Evans RM, 1982. Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300: 611–615.

    Article  CAS  PubMed  Google Scholar 

  • Paradis K, Langford G, Long Z, Heneine W, Sandstrom P, Switzer WM, et al. 1999. Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group. Science 285: 1236–1241.

    Article  CAS  PubMed  Google Scholar 

  • Patience C, Patton GS, Takeuchi Y, Weiss RA, McClure MO, Rydberg L, Breimer ME, 1998. No evidence of pig DNA or retroviral infection in patients with short-term extracorporeal connection to pig kidneys. Lancet 352: 699–701.

    Article  CAS  PubMed  Google Scholar 

  • Patience C, Takeuchi Y, Weiss RA, 1997. Infection of human cells by an endogenous retrovirus of pigs. Nat Med 3: 282–286.

    Article  CAS  PubMed  Google Scholar 

  • Petters RM, Alexander CA, Wells KD, Collins EB, Sommer JR, Blanton MR, et al. 1997. Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa. Nat Biotechnol 15: 965–970.

    Article  CAS  PubMed  Google Scholar 

  • Phelps CJ, Koike C, Vaught TD, Boone J, Wells KD, Chen SH, et al. 2003. Production of alpha 1,3-galactosyltransferase-deficient pigs. Science 299: 411–414.

    Article  CAS  PubMed  Google Scholar 

  • Polejaeva IA, Campbell KH, 2000. New advances in somatic cell nuclear transfer: application in transgenesis. Theriogenology 53: 117–126.

    Article  CAS  PubMed  Google Scholar 

  • Powell BC, Walker SK, Bawden CS, Sivaprasad AV, Rogers GE, 1994. Transgenic sheep and wool growth: possibilities and current status. Reprod Fertil Dev 6: 615–623.

    Article  CAS  PubMed  Google Scholar 

  • Pursel VG, Pinkert CA, Miller KF, Bolt DJ, Campbell RG, Palmiter RD, 1989. Genetic engineering of livestock. Science 244: 1281–1288.

    Article  CAS  PubMed  Google Scholar 

  • Rieth A, Pothier F, Sirard MA, 2000. Electroporation of bovine spermatozoa to carry DNA containing highly repetitive sequences into oocytes and detection of homologous recombination events. Molecular Reproduction and Development 57: 338–345.

    Article  CAS  PubMed  Google Scholar 

  • Robertson E, Bradley A, Kuehn M, Evans M, 1986. Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature 323: 445–448.

    Article  CAS  PubMed  Google Scholar 

  • Rudolph KL, Millard M, Bosenberg MW, DePinho RA, 2001. Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet 28: 155–159.

    Article  CAS  PubMed  Google Scholar 

  • Rudolph NS, 1999. Biopharmaceutical production in transgenic livestock. Trends Biotechnol 17: 367–374.

    Article  CAS  PubMed  Google Scholar 

  • Saito S, Sawai K, Ugai H, Moriyasu S, Minamihashi A, Yamamoto Y, et al. 2003. Generation of cloned calves and transgenic chimeric embryos from bovine embryonic stem-like cells. Biochem Biophys Res Commun 309: 104–113.

    Article  CAS  PubMed  Google Scholar 

  • Schnieke AE, Kind AJ, Ritchie WA, Mycock K, Scott AR, Ritchie M, Wilmut I, et al. 1997. Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278: 2130–2133.

    Article  CAS  PubMed  Google Scholar 

  • Seidel GE, Jr., 1993. Resource requirements for transgenic livestock research. J Anim Sci 71: 26–33.

    PubMed  Google Scholar 

  • Shiels PG, Kind AJ, Campbell KH, Waddington D, Wilmut I, Colman A, Schnieke AE, 1999. Analysis of telomere lengths in cloned sheep. Nature 399: 316–317.

    Article  CAS  PubMed  Google Scholar 

  • Shim H, Gutierrez-Adan A, Chen LR, BonDurant RH, Behboodi E, Anderson GB, 1997. Isolation of pluripotent stem cells from cultured porcine primordial germ cells. Biol Reprod 57: 1089–1095.

    Article  CAS  PubMed  Google Scholar 

  • Sikes ML, O’Malley BW, Jr., Finegold MJ, Ledley FD, 1994. In vivo gene transfer into rabbit thyroid follicular cells by direct DNA injection. Hum Gene Ther 5: 837–844.

    Article  CAS  PubMed  Google Scholar 

  • Soukka T, Tenovuo J, Lenander-Lumikari M, 1992. Fungicidal effect of human lactoferrin against Candida albicans. FEMS Microbiol Lett 69: 223–228.

    Article  CAS  PubMed  Google Scholar 

  • Souza T, MacDougall C, Campbell BK, McNeilly AS, Baird DT, 2001. The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPR1B) gene. J Endocrinol 169: R1–6.

    Article  CAS  PubMed  Google Scholar 

  • Stacey A, Schnieke A, Kerr M, Scott A, McKee C, Cottingham I, et al. 1995. Lactation is disrupted by alpha-lactalbumin deficiency and can be restored by human alpha-lactalbumin gene replacement in mice. Proc Natl Acad Sci USA 92: 2835–2839.

    Article  CAS  PubMed  Google Scholar 

  • Stinnakre MG, Vilotte JL, Soulier S, Mercier JC, 1994. Creation and phenotypic analysis of alpha-lactalbumin-deficient mice. Proc Natl Acad USA 91: 6544–6548.

    Article  CAS  Google Scholar 

  • Suda O, Smith LA, d’Uscio LV, Peterson TE, Katusic ZS, 2005. In vivo expression of recombinant vascular endothelial growth factor in rabbit carotid artery increases production of superoxide anion. Arterioscler Thromb Vasc Biol 25: 506–511.

    Article  CAS  PubMed  Google Scholar 

  • Sullivan EJ, Kasinathan S, Kasinathan P, Robl JM, Collas P, 2004. Cloned calves from chromatin remodeled in vitro. Biol Reprod 70: 146–153.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Van Berkel PH, Welling MM, Geerts M, van Veen HA, Ravensbergen B, Salaheddine M, et al. 2002. Large scale production of recombinant human lactoferrin in the milk of transgenic cows. Nat Biotechnol 20: 484–487.

    Article  PubMed  CAS  Google Scholar 

  • Van Doorn MB, Burggraaf J, van Dam T, Eerenberg A, Levi M, Hack CE, et al. 2005. A phase I study of recombinant human C1 inhibitor in asymptomatic patients with hereditary angioedema. J Allergy Clin Immunol 116: 876–883.

    Article  PubMed  CAS  Google Scholar 

  • Velander WH, Johnson JL, Page RL, Russell CG, Subramanian A, Wilkins TD, et al. 1992. High-level expression of a heterologous protein in the milk of transgenic swine using the cDNA encoding human protein C. Proc Natl Acad Sci USA 89: 12003–12007.

    Article  CAS  PubMed  Google Scholar 

  • Wakayama T, Shinkai Y, Tamashiro KL, Niida H, Blanchard DC, Blanchard RJ, et al. 2000. Cloning of mice to six generations. Nature 407: 318–319.

    Article  CAS  PubMed  Google Scholar 

  • Wall RJ, Kerr DE, Bondioli KR, 1997. Transgenic dairy cattle: genetic engineering on a large scale. J Dairy Sci 80: 2213–2224.

    Article  CAS  PubMed  Google Scholar 

  • Wall RJ, Powell AM, Paape MJ, Kerr DE, Bannerman DD, Pursel VG, 2005. Genetically enhanced cows resist intramammary Staphylococcus aureus infection. Nat Biotechnol 23: 445–451.

    Article  CAS  PubMed  Google Scholar 

  • Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, et al. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562.

    Article  CAS  PubMed  Google Scholar 

  • Weissmann C, Enari M, Klohn PC, Rossi D, Flechsing E, 2002. Transmission of prions. Proc Natl Acad Sci USA 99: 16378–16383.

    Article  CAS  PubMed  Google Scholar 

  • Wheeler MB, 2003. Production of transgenic livestock: promise fulfilled. J Anim Sci 81: 32–37.

    CAS  PubMed  Google Scholar 

  • Willadsen SM, 1986. Nuclear transplantation in sheep embryos. Nature 320: 63–65.

    Article  CAS  PubMed  Google Scholar 

  • Williams RS, Johnston SA, Riedy M, DeVit MJ, McElligott SG, Sanford JC, 1991. Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles. Proc Natl Acad Sci USA 88: 2726–2730.

    Article  CAS  PubMed  Google Scholar 

  • Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH, 1997. Viable offspring derived from fetal and adult mammalian cells. Nature 385: 810–813.

    Article  CAS  PubMed  Google Scholar 

  • Wobus AM, Boheler KR, 2005. Embryonic stem cells: prospects for developmental biology and cell therapy. Physiol Rev 85: 635–678.

    Article  CAS  PubMed  Google Scholar 

  • Wright G, Carver A, Cottom D, Reeves D, Scot A, Simons P, et al. 1991. High level expression of active human alpha-1-antitrypsin in the milk of transgenic sheep. Biotechnology (NY) 9: 830–834.

    Article  CAS  Google Scholar 

  • Zaidi A, Schmoeckel M, Bhatti F, Waterworth P, Tolan M, Cozzi E, et al. 1998. Life-supporting pig-to-primate renal xenotransplantation using genetically modified donors. Transplantation 65: 1584–1590.

    Article  CAS  PubMed  Google Scholar 

  • Zawada WM, Cibelli JB, Choi PK, Clarkson ED, Golueke PJ, Witta SE, et al. 1998. Somatic cell cloned transgenic bovine neurons for transplantation in parkinsonian rats. Nat Med 4: 569–574.

    Article  CAS  PubMed  Google Scholar 

  • Zbikowska HM, Soukhareva N, Behnam R, Chang R, Drews R, Lubon H, et al. 2002a. The use of the uromodulin promoter to target production of recombinant proteins into urine of transgenic animals. Transgenic Res 11: 425–435.

    Article  CAS  PubMed  Google Scholar 

  • Zbikowska HM, Soukhareva N, Behnam R, Lubon H, Hammond D, Soukharev S, 2002b. Uromodulin promoter directs high-level expression of biologically active human alpha1-antitrypsin into mouse urine. Biochem J 365: 7–11.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. EMBRAPA Genetic Resources and Biotechnology, Av. W/5, Norte Final, PBI, Sala 7B, CEP 70770-900, Brasilia, DF, Brazil

    Eduardo O. Melo, Aurea M. O. Canavessi, Mauricio M. Franco & Rodolfo Rumpf

Authors
  1. Eduardo O. Melo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aurea M. O. Canavessi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mauricio M. Franco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rodolfo Rumpf
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eduardo O. Melo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Melo, E.O., Canavessi, A.M.O., Franco, M.M. et al. Animal transgenesis: state of the art and applications. J Appl Genet 48, 47–61 (2007). https://doi.org/10.1007/BF03194657

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03194657

Keywords

Search

Navigation