Transgenic perspectives in livestock science: a review
M. B. Nottle A B C , A. C. Boquest A , S. J. Harrison A , C. G. Grupen A , R. A. Faast A , R. J. Ashman A and S. M. McIlfatrick AA Reproductive Biotechnology Division, BresaGen Limited, PO Box 259 Rundle Mall, Adelaide, SA 5000, Australia.
B Present address: Department of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia.
C Corresponding author. Email: mark.nottle@adelaide.edu.au
Australian Journal of Experimental Agriculture 44(11) 1113-1117 https://doi.org/10.1071/EA03237
Submitted: 16 November 2003 Accepted: 2 April 2004 Published: 14 December 2004
Abstract
The limitations of existing transgenic technology, the potential of cloning technology to overcome these, as well as technologies which may be available in the future for inserting new genetic material are discussed. Currently, transgenic livestock are produced by injecting hundreds to thousands of copies of a particular transgene into the pronucleus of a fertilised egg. This method suffers from a number of inherent limitations that prevent the full potential of this technology from being explored. Most of these limitations stem from the fact that it is impossible to control the site at which the transgene becomes inserted. Transgenic technology holds considerable promise for the livestock industries as well as having important biomedical applications. However, before any of these possibilities can be realised, technology is required whereby a single copy of a particular transgene can be inserted or ‘knocked in’ at a site that does not interfere with expression, as well as having the capacity to ‘knockout’ existing genes. This is possible in mice using a combination of homologous recombination and embryonic stem cell technologies. However, despite considerable effort worldwide, embryonic stem cells are yet to be isolated from any of the livestock species. The ability to clone these now means that somatic cells most notably fetal fibroblasts, can used for gene targeting purposes instead of embryonic stem cells. However, this method is not without its limitations and it is possible that more efficient methods will be developed in the future. In particular, the use of mammalian artificial chromosomes will extend this technology to allow combinations of transgenes as well as chromosomal segments to be incorporated, allowing us to explore the full potential of transgenic technology for agricultural as well as biomedical applications.
Acknowledgment
We thank Dr Peter Wigley for critically reading the manuscript.
Apice AJF,
Nottle MB, Cowan PJ
(2001) Genetic modification for xenotransplantation: transgneics and donors. Transplantation Proceedings 33, 3053–3054.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Chan AW,
Homan EJ,
Ballou LU,
Burns JC, Bremel RD
(1998) Transgenic cattle produced by reverse-transcribed gene transfer in oocytes. Proceedings of the National Academy of Sciences of the United States of America 95, 14028–14033.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Cibelli JB,
Stice SL,
Golueke PJ,
Kane JJ,
Jerry J,
Blackwell C,
Ponce de Leon FA, Robl JM
(1998) Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280, 1256–1258.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Dai Y,
Vaught TD,
Boone J,
Chen SH, Phelps CJ , et al.
(2002) Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs. Nature Biotechnology 20, 251–255.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Harrison SJ,
Guidolin A,
Faast R,
Crocker LA,
Giannakis C,
d’Apice AJ,
Nottle MB, Lyons I
(2002) Efficient generation of alpha (1,3) galactosyltransferase knockout porcine fetal fibroblasts for nuclear transfer. Transgenic Research 11, 143–150.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Hill JR,
Roussel AJ,
Cibelli JB,
Edwards JF, Hooper NL , et al.
(1999) Clinical and pathological features of cloned transgenic calves and fetuses (13 case studies). Theriogenology 51, 1451–1465.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Keefer CL,
Baldassare H,
Keyston R,
Wang B, Bhatia B , et al.
(2001) Genenration of dwarf goat (Capra hircus) clones following nuclear transfer with transfected and non transfected fetal fibroblasts and in vitro matured oocytes. Biology of Reproduction 64, 849–856.
| Crossref |
PubMed |
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. Biochemical and Biophysical Research Communications 222, 742–747.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Kuroiwa Y,
Kasinathan P,
Choi YJ,
Naeem R, Tomizuka K , et al.
(2002) Cloned transchromosmic calves producing human immunoglobulin. Nature Biotechnology 20, 889–894.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lai L,
Kolber-Simonds D,
Park KW,
Cheong HT, Greenstein JL , et al.
(2002) Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295, 1089–1092.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lauth M,
Moerl K,
Barski JJ, Meyer M
(2000) Characterization of Cre-mediated cassette exchange after plasmid microinjection in fertilized mouse oocytes. Genesis 27, 153–158.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lavitrano M,
Bacci ML,
Forni M,
Lazzereschi D, Stefano CD , et al.
(2002) Efficient production by sperm-mediated gene transfer of human decay accelerating factor (hDAF) transgenic pigs for xenotransplantation. Proceedings of the National Academy of Sciences of the United States of America 99, 14230–14235.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lavitrano M,
Camaioni A,
Fazio VM,
Dolci S,
Farace MG, Spadafora C
(1989) Sperm cells as vectors for introducing foreign DNA into eggs: genetic transformation of mice. Cell 57, 717–723.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Martin DIK, Whitelaw E
(1996) The vagaries of variegating transgenes. BioEssays 18, 919–923.
| Crossref |
PubMed |
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.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Nottle MB,
Haskard KA,
Verma PJ,
Du ZT, Grupen CG , et al.
(2001) Effect of DNA concentration on transgenesis rates in mice and pigs. Transgenic Research 10, 523–531.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Onishi A,
Iwamoto M,
Akita T,
Miukawa S,
Takeda K,
Awata T,
Hanada H, Perry AC
(2000) Pig cloning by microinjection of fetal fibroblast nuclei. Science 289, 1188–1190.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Sauer B
(1998) Inducible gene targeting in mice using the Cre/lox system. Methods 14, 381–392.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Stewart CL,
Vanek M, Wagner EF
(1985) Expression of foreign genes from retroviral vectors in mouse teratocarcinoma chimaeras. Journal of European Molecular Biology Organisation 4, 3701–3709.
Wigley P,
Becker C,
Beltrame J,
Blake T, Cocker C , et al.
(1994) Site specific transgene insertion: an approach. Reproduction, Fertility and Development 6, 585–586.
| Crossref |
Wilmut I,
Schnieke AE,
McWhir J,
Kind AJ, Campbell KHS
(1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810–813.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wilmut I,
Beaujean N,
De Sousa PA,
Dinnyes A,
King TJ,
Patterson LA,
Wells DN, Young LE
(2002) Somatic cell nuclear transfer. Nature 419, 583–587.
| Crossref | GoogleScholarGoogle Scholar | PubMed |