Skip to main content

Development of Germline Manipulation Technologies in Livestock

  • Conference paper
  • 1343 Accesses

Abstract

Genetic improvement by conventional breeding is restricted to those genetic loci present in the parental breeding individuals. Gene addition through transgenic technology offers a route to overcome this restriction. The transgene can be introduced into the germ cells or the fertilized zygote, using viral vectors, by simple co-culture or direct micro-injection. Alternatively, the transgene can be incorporated into a somatic cell, which is then incorporated into a developing embryo. This latter approach allows gene-targeting strategies to be employed. Using pronuclear injection methods, transgenic livestock have been generated with the aim of enhancing breeding traits of agricultural importance, or for biomedical applications. Neither has been taken beyond the development phase. Before they are, in addition to issues of commercial development, basic technological issues addressing inefficiency and complexity of the methodology need to be overcome, and appropriate gene targets identified. At the moment, perhaps the most encouraging development involves the use of viral vectors that offer increased simplicity and efficiency. By combining this new technology with transgenes that evoke the powerful intracellular machinery involved in RNA interference, pioneering applications to generate animals that are less susceptible to infectious disease may be possible.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Brinster, R.L., Sandgren, E.P., Behringer, R.R. & Palmiter, R.D. 1989. No simple solution for making transgenic mice. Cell, 59: 239–241.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Campbell. K.H., McWhir, J., Ritchie, W.A. & Wilmut, I. 1996. Sheep cloned by nuclear transfer from a cultured cell line. Nature, 380: 64–68.

    PubMed  CAS  ISI  Google Scholar 

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

    PubMed  CAS  ISI  Google Scholar 

  • Chan, A.W., Chong, K.Y., Martinovich, C., Simerly, C. & Schatten, G. 2001. Transgenic monkeys produced by retroviral gene transfer into mature oocytes. Science, 291: 309–312.

    PubMed  CAS  ISI  Google Scholar 

  • Chan, A.W., Homan, E.J., Ballou, L.U., Burns, J.C. & Bremel, R.D. 1998. Transgenic cattle produced by reverse-transcribed gene transfer in oocytes. Proceedings of the National Academy of Sciences, USA, 95: 14028–14033.

    CAS  Google Scholar 

  • Clark, A.J. & Whitelaw, C.B.A. 2003. A future for transgenic livestock. Nature Reviews Genetics, 4: 825–833.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Clark, A.J., Bessos, H., Bishop, J.O., Brown, P., Harris, S., Lathe, R., McClenaghan, M., Prowse, C., Simons, J.P., Whitelaw, C.B.A. & Wilmut, I. 1989. Expression of human anti-hemophilic factor IX in the milk of transgenic sheep. Biotechnology, 7: 487–492.

    CAS  Google Scholar 

  • Damak, S., Jay, N.P., Barrell, G.K. & Bullock, D.W. 1996. Targeting gene expression to the wool follicle in transgenic sheep. Biotechnology, 14: 18118–18114.

    Google Scholar 

  • Denning, C., Burl, S., Ainslie, A., Bracken, J., Dinnyes, A., Fletcher, J., King, T., Ritchie, M., Ritchie, W.A., Rollo, M., de Sousa, P., Travers, A., Wilmut, I. & Clark, A.J. 2001a. Deletion of the alpha(1,3)galactosyl transferase (GGTA1) gene and the prion protein (PrP)gene in sheep. Nature Biotechnology, 19: 529–530.

    Article  Google Scholar 

  • Denning, C., Dickinson, P., Burl, S., Wylie, D., Fletcher, J. & Clark, A.J. 2001b. Gene targeting in sheep and pig primary fetal fibroblasts. Cloning Stem Cells, 3: 205–215.

    Article  Google Scholar 

  • Fodor, W.L., Williams, B.L., Matis, L.A., Madri, J.A., Rollins, S.A., Knight, J.W., Velander, W. & Squinto, S.P. 1994. Expression of a functional human complement inhibitor in a transgenic pig as a model for the prevention of xenogeneic hyperacute organ rejection. Proceedings of the National Academy of Sciences, USA, 91: 11153–11157.

    CAS  Google Scholar 

  • Gamma, L.T., Smith, C. & Gibson, J.P. 1992. Transgene effects, introgression strategies and testing schemes in pigs. Animal Production, 54: 427–440.

    Google Scholar 

  • Golovan, S.P., Meidinger, R.G., Ajakaiye, A., Cottrill, M., Wiederkehr, M.Z., Barney, D.J., Plante, C., Pollard, J.W., Fan, M.Z., Hayes, M.A., Laursen, J., Hjorth, J.P., Hacker, R.R., Phillips, J.P. & Forsberg, C.W. 2001. Pigs expressing salivary phytase produce low-phosphorus manure. Nature Biotechnology, 19: 741–745.

    PubMed  CAS  ISI  Google Scholar 

  • Gordon, J.W. 2002. High toxicity, low receptor density, and low integration frequency severely impede the use of adenovirus vectors for production of transgenic mice. Biology of Reproduction, 67: 1172–1179.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Gordon, J.W. & Ruddle, F.H. 1981. Integration and stable germ line transmission of genes injected into mouse pronuclei. Science, 214: 1244–1246.

    PubMed  CAS  ISI  Google Scholar 

  • Hammer, R.E., Pursel, V.G., Rexroad, C.E., Wall, R.J., Bolt, D.J., Ebert, K.M., Palmiter, R.D. & Brinster, R.L. 1985. Production of transgenic rabbits, sheep and pigs by microinjection. Nature, 315: 680–683.

    PubMed  CAS  ISI  Google Scholar 

  • Hannon, G.J. 2002. RNA interference. Nature, 418: 244–251.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Houdebine, L.M. 2000. Transgenic animal bioreactors. Transgenic Research, 9: 305–320.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Jahner, D. & Jaenisch, R. 1985. Terovirus-induced de novo methylation of flanking host sequences correlates with gene inactivity. Nature, 315: 594–597.

    PubMed  CAS  ISI  Google Scholar 

  • Lavitrano, M., Camaioni, A., Fazio, V.M., Dolci, S., Farace, M.G. & Spadafora, C. 1989. Sperm cells as vectors for introducing foreign DNA into eggs: genetic transformation of mice. Cell, 57: 717–723.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Logan, A.C., Lutzko, C. & Kohn, D.B. 2002. Advances in lentiviral vector design for gene-modification of hematopoetic stem cells. Current Opinions in Biotechnology, 13: 429–436.

    CAS  Google Scholar 

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

    Article  PubMed  CAS  ISI  Google Scholar 

  • McCreath, K.J., Howcroft, J., Campbell, K.H., Colman, A., Schneike, A.E. & Kind, A.J. 2000. Production of gene-targeted sheep by nuclear transfer from cultured somatic cells. Nature, 405: 1066–1069.

    PubMed  CAS  ISI  Google Scholar 

  • McManus, M.T. & Sharp, P.A. 2002. Gene silencing in mammals by small interfering RNAs. Nature Reviews Genetics, 3: 737–747.

    Article  PubMed  CAS  ISI  Google Scholar 

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

    PubMed  CAS  ISI  Google Scholar 

  • Nottle, M.B., Haskard, K.A., Verma, P.J., Du, Z.T., Grupen, C.G., McIlfatrick, S.M., Ashman, R.J., Harrison, S.J., Barlow, H., Wigley, P.L., Lyons, I.G., Cowan, P.J., Crawford, R.J., Tolstoshev, P.L., Pearse, M.J., Robins, A.J. & d’Apice, A.J. 2001. Effect of DNA concentration on transgenesis rates in mice and pigs. Transgenic Research, 10: 523–551.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Palmiter, R.D., Brinster, R.L., Hammer, R.E., Trumbauer, M.E., Rosenfeld, M.G., Birnberg, N.C. & Evans, R.M. 1992. Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature, 300: 611–615.

    Google Scholar 

  • Pfeifer, A., Ikawa, M., Dyn, Y. & Verma, I.M. 2002. Transgenesis by lentiviral vectors: lack of gene silencing in mammalian embryonic stem cells and pre-implantation embryos. Proceedings of the National Academy of Sciences, USA, 99: 2140–2145.

    Article  CAS  Google Scholar 

  • Phelps, C.J., Koike, C., Vaught, T.D., Boone, J., Wells, K.D., Chen, S.H., Ball, S., Specht, S.M., Poljaeva, I.A., Monahan, J.A., Jobst, P.M., Sharma, S.B., Lamborn, A.E., Garst, A.A., Moore, M., Demetris, A.J., Rudert, W.A., Bottino, R., Bertera, S., Truco, M., Starzl, T.E., Dai, Y. & Ayares, D.L. 2003. Production of alpha 1,3 galactosyl-transferase deficient-pigs. Science, 299: 411–414.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Pursel, V.G., Pinkert, C.A., Miller, K.F., Volt, D.J., Campbell, R.G., Palmiter, R.D., Brinster, R.L. & Hammer, R.E. 1989. Genetic engineering of livestock. Science, 244: 1281–1288.

    PubMed  CAS  ISI  Google Scholar 

  • Smithies, O., Gregg, R.G., Boggs, S.S., Koralewski, M.A. & Kucherlapati, R.S. 1985. Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination. Nature, 317: 230–234.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Stice, S.L. 2002. Opportunities and challenges in domestic animal embryonic stem cell research. pp. 64–71, in: A.J. Clark (ed). Animal Breeding: Technology for the 21st Century. Switzerland: Harwood Academic Press.

    Google Scholar 

  • Thomas, C.E., Ehrhardt, A. & Kay, M.A. 2002. Progress and problems with the use of viral vectors for gene therapy. Nature Reviews Genetics, 4: 346–358.

    ISI  Google Scholar 

  • Tiscornia, G., Singer, O., Ikawa, M. & Verma, I.M. 2003. A general method for gene knockdown in mice by using lentiviral vectors expressing small interfering RNA. Proceedings of the National Academy of Sciences, USA, 100: 1844–1848.

    Article  CAS  Google Scholar 

  • Wilmut, I. 2002. Are there any normal cloned mammals? Nature Medicine, 8: 215–216.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Wilmut, I. & Whitelaw, C.B.A. 1994. Strategies for the production of pharmaceuticals in milk. Reproduction Fertility and Development, 6: 625–630.

    Article  CAS  ISI  Google Scholar 

  • Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J. & Campbell, K.H. 1997. Viable offspring derived from fetal and adult mammalian cells. Nature, 385: 810–813.

    Article  PubMed  CAS  ISI  Google Scholar 

  • Wright, G., Carver, A., Cottom, D., Reeves, D., Scott, A., Simons, P., Wilmut, I., Garner, I. & Colman, A. 1991. High level expression of active human alpha-1-antitrypsin in the milk of transgenic sheep. Biotechnology, 9: 830–834.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 IAEA

About this paper

Cite this paper

Bruce, C., Whitelaw, A. (2005). Development of Germline Manipulation Technologies in Livestock. In: Makkar, H.P., Viljoen, G.J. (eds) Applications of Gene-Based Technologies for Improving Animal Production and Health in Developing Countries. Springer, Dordrecht. https://doi.org/10.1007/1-4020-3312-5_9

Download citation

Publish with us

Policies and ethics