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RESEARCH ARTICLE

Commercial aspects of cloning and genetic modification in cattle

I. M. Lewis B C , A. J. French A C , R. T. Tecirlioglu A C , G. Vajta F , A. E. McClintock A B , K. R. Nicholas D , K. A. Zuelke E , M. K. Holland A C and A. O. Trounson A C
+ Author Affiliations
- Author Affiliations

A Cooperative Research Centre for Innovative Dairy Products (Dairy CRC), Level 1, 84 William Street, Melbourne, Vic. 3000, Australia.

B Genetics Australia Cooperative Ltd, Woolpack Road, Bacchus Marsh, Vic. 3340, Australia.

C Centre for Early Human Development, Monash Institute of Reproduction and Development, Monash University, 27–31 Wright Street, Clayton, Vic. 3168, Australia.

D Department of Zoology, University of Melbourne, Parkville, Vic. 3010, Australia.

E United States Department of Agriculture, ARS Germplasm Laboratory, Belstville, MD 20705, USA.

F Section of Reproductive Biology, Department of Animal Breeding and Genetics, Danish Institute of Agricultural Sciences, Tjele, Denmark.

G Corresponding author. Email: ilewis@genaust.com.au

Australian Journal of Experimental Agriculture 44(11) 1105-1111 https://doi.org/10.1071/EA03239
Submitted: 16 November 2003  Accepted: 1 April 2004   Published: 14 December 2004

Abstract

A range of potential commercial applications of cloning and genetic modification in cattle has been suggested over the last decade. It includes the rapid multiplication of elite genotypes, production of valuable human proteins, altered production characteristics, increased disease resistance and milk with improved nutritional value and processing capabilities. However, an economic return from the sale of product is far from reality in any of these areas. One impediment to achieving economic sustainability is the extremely low efficiency in producing healthy offspring from transferred cloned embryos. Other significant impediments are societal concerns surrounding such technologies, animal welfare issues and regulatory requirements. This review will focus on current biological limitations and technical capabilities in commercial settings, the changes required to allow the production and sale of products at economically sustainable levels, cryopreservation and the progress towards automation of cloning techniques.


Acknowledgments

We acknowledge the numerous scientific, technical and administrative staff at the Monash Institute of Reproduction and Development, Genetics Australia Cooperative Ltd and the Victorian Institute of Animal Science, whose dedicated work over the last 12 years has helped significantly to progress the technologies discussed in this review towards large-scale application.


References


Anderson GB, Seidel GE (1998) Cloning for profit. Science 280, 1400–1401.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Beebe D, Wheeler M, Zeringue H, Walters E (2002) Microfluidic technology for assisted reproduction Theriogenology 57, 125–135.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Behboodi E, Anderson GB, BonDurant RH, Cargill SK, Kreuscher BR, Medrano JF, Murray JD (1995) Birth of large calves that developed from in vitro-derived bovine embryos. Theriogenology 44, 227–232.
Crossref | GoogleScholarGoogle Scholar | open url image1

Booth PJ, Tan SJ, Reipurth R, Holm P, Callesen H (2001) Simplification of bovine somatic cell transfer by application of a zona-free manipulation technique. Cloning and Stem Cells 3, 139–150.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Briggs R, King TJ (1952) Transplantation of living nuclei from blastula cells into enucleated frog’s eggs. Proceedings of the National Academy of Sciences of the United States of America 38, 455–463. open url image1

Brink MF, Bishop MD, Pieper FR (2000) Developing efficient strategies for the generation of transgenic cattle which produce biopharmaceuticals in milk. Theriogenology 53, 139–141.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Brophy B, Smolenski G, Wheeler T, Wells D, L’Huillier P, Laible G (2003) Cloned transgenic cattle produce milk with higher levels of β-casein and κ-casein. Nature Biotechnology 21, 157–162.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Campbell KHS (1999) Nuclear equivalence, nuclear transfer and the cell cycle. Cloning 1, 3–15.
Crossref | GoogleScholarGoogle Scholar | open url image1

Campbell KHS, McWhir J, Ritchie WA, Wilmut I (1996) Sheep cloned by nuclear transfer from a cultured cell line. Nature 380, 64–66.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Capecchi MR (2000) How close are we to implementing gene targeting in the animals other than the mouse? Proceedings of the National Academy of Sciences of the United States of America 97, 956–957.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Cezar GG (2003) Epigenetic reprogramming of cloned animals. Cloning and Stem Cells 5, 165–179.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Cibelli JB, Campbell KH, Seidel GE, West MD, Lanza RP (2002) The health profile of cloned animals. Nature Biotechnology 20, 13–14.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Ponce de Leon FA, Robl JM (1998) Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280, 1256–1258.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Cormick C (2003) Causes of public concern in Australia. International Journal of Biotechnology 5, 95–104. open url image1

Daniels R, Hall V, Trounson AO (2000) Analysis of gene transcription in nuclear transfer embryos reconstructed with granulosa cell nuclei. Biology of Reproduction 63, 1034–1040.
PubMed |
open url image1

Dinnyes A, De Sousa P, King T, Wilmut I (2002) Somatic cell nuclear transfer: recent progress and challenges. Cloning and Stem Cells 4, 81–90.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Faber DC, Molina JA, Ohlrichs CL, Vander Zwaag DF, Ferne LB (2003) Commercialization of animal biotechnology. Theriogenology 59, 125–138.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Farin PW, Farin CE (1995) Transfer of bovine embryos produced in vivo or in vitro: survival and fetal development. Biology of Reproduction 52, 676–682.
PubMed |
open url image1

French AJ, Lewis IM, Ruddock NT, Korfiatis NK, Hall VJ , et al. (2003) Generation of αS1 casein gene transgenic calves by nuclear transfer. Biology of Reproduction Suppl. 68, 240. open url image1

Galli C, Duchi R, Crotti Turini P, Ponderato N, Colleoni S, Lagutina I, Lazzari G (2003) Bovine embryo technologies. Theriogenology 59, 599–616.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Garry FB, Adams R, McCann JP, Odde KG (1996) Postnatal characteristics of calves produced by nuclear transfer cloning. Theriogenology 45, 141–152.
Crossref | GoogleScholarGoogle Scholar | open url image1

Gurdon JB, Elsdale TR, Fischberg M (1958) Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei. Nature 182, 64–65.
PubMed |
open url image1

Hakelien AM, Landsverk HB, Robl JM, Skalhegg BS, Collas P (2002) Reprogramming fibroblasts to express T-cell functions using cell extracts. Nature Biotechnology 20, 460–466.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Hasler JF, Henderson WB, Hurtgen JP, Jin ZQ, McCauley AD, Mower SA, Neely B, Shuey LS, Stokes JE, Trimmer SA (1995) Production, freezing and transfer of bovine IVF embryos and subsequent calving results. Theriogenology 43, 141–152.
Crossref | GoogleScholarGoogle Scholar | open url image1

Henderson AKW (1998) Northern Australian cattle production systems. In ‘Proceedings of the World Association for Buiatrics Congress’. (Ed. IW Caple) pp. 5–9. (Australian Association of Cattle Veterinarians)

Hill JR, Rousell 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 | open url image1

Hill JR, Burghardt RC, Jones K, Long CR, Looney CR, Shin T, Spencer TE, Thompson JA, Winger QA, Westhusin ME (2000) Evidence for placental abnormality as the major cause of mortality in first trimester somatic cell cloned bovine foetuses. Biology of Reproduction 63, 1787–1794.
PubMed |
open url image1

Jacobsen H, Schmidt M, Holm P, Sangild PT, Vajta G, Greve T, Callesen H (2000) Body dimensions and birth and organ weights of calves derived from in vitro produced embryos cultured with or without serum and oviduct epithelium cells. Theriogenology 53, 1761–1769.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Kato Y, Tany T, Sotomaru Y, Kurokawa K, Kato J, Doguchi H, Yasue H, Tsunoda Y (1998) Eight calves cloned from somatic cells of a single adult. Science 282, 2095–2098.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Jaenisch R, Eggan K, Humpherys D, Rideout W, Hochedlinger K (2002) Nuclear cloning, stem cells, and genomic reprogramming. Cloning and Stem Cells 4, 389–396.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Kubota C, Yamakuchi H, Todoroki J, Mizoshita K, Tabara N, Barber M, Yang X (2000) Six cloned calves produced from adult fibroblast cells after long-term culture. Proceedings of the National Academy of Sciences of the United States of America 97, 990–995.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Lewis IM, Peura TT, Trounson AO (1998) Large-scale applications of cloning for agriculture: an industry perspective. Reproduction, Fertility and Development 10, 677–681.
Crossref | GoogleScholarGoogle Scholar | open url image1

Lewis IM, Peura TT, Owens JL, Ryan MF, Diamente MG, Pushett DA, Lane MW, Jenkin G, Coleman PJ, Trounson AO (2000) Outcomes from novel, simplified nuclear transfer techniques in cattle. Theriogenology 53, 233. open url image1

Lewis IM, Munsie MJ, French AJ, Daniels R, Trounson AO (2001) The cloning cycle: from amphibia to mammals and back. Reproductive Medicine Review 9, 3–33.
Crossref | GoogleScholarGoogle Scholar | open url image1

Lewis IM, Vajta G, Tercirlioglu T (2001) b International Patent. A method of nuclear transfer. PCT/4AU02/00491.

McClintock AE (1998) Impact of cloning on cattle breeding systems. Reproduction, Fertility and Development 10, 667–669.
Crossref | GoogleScholarGoogle Scholar | open url image1

Niemann H, Kues WA (2000) Transgenic livestock: premises and promises. Animal Reproduction Science 60–61, 277–293.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Oback B, Wiersema AT, Gaynor P, Laible G, Tucker FC , et al. (2003) Cloned cattle derived from a novel, zona-free embryo reconstruction system. Cloning and Stem Cells 5, 3–12.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Pace MM, Augenstein ML, Betthauser JM, Childs L, Eilertsen KJ , et al. (2002) Ontogeny of cloned cattle to lactation. Biology of Reproduction 67, 334–339.
PubMed |
open url image1

Peterson AJ, McMillan WH (1998) Allantoic aplasia — a consequence of in vitro production of bovine embryos and the major cause of late gestation embryo loss. Proceedings of the Australian Society for Reproductive Biology 29, 4. open url image1

Peterson AJ, McMillan WH (1998) Variation in the rate of emergence of the bovine allantois. Proceedings of the Australian Society for Reproductive Biology 29, 63. open url image1

Peura TT, Lewis IM, Trounson AO (1998) The effect of recipient oocyte volume on nuclear transfer in cattle. Molecular Reproduction and Development 50, 185–189.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Renard JP, Zhou Q, LeBourhis D, Chavatte-Palmer P, Hue I, Heyman Y, Vignon X (2002) Nuclear transfer technologies: between successes and doubts. Theriogenology 57, 203–222.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Renard JP, Chastant S, Chesne P, Richard C, Marchel J, Cordonnier N, Chavatte P, Vignon X (1999) Lymphoid hypoplasia and somatic cloning. Lancet 353, 1489–1491.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Rideout WM, Eggan K, Jaenisch R (2001) Nuclear cloning and epigenetic reprogramming of the genome. Science 293, 1093–1098.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Schnieke AE, Kind AJ, Ritchie WA, Mycock K, Scott AR, Ritchie M, Wilmut I (1997) Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278, 2130–2133.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Seidel GE (2001) Cloning, transgenesis and genetic variance in animals. Cloning and Stem Cells 3, 251–256.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Shimozowa N, Ono Y, Kimoto S, Hioko K, Araki Y, Shinkai Y, Kono Ito M (2002) Abnormalities in cloned mice are not transmitted to the progeny. Genesis 34, 203–207.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Sinclair KD, Broadbent PJ, Dolman DF (1995) In vitro produced embryos as a means of achieving pregnancy and improving productivity in beef cows. Journal of Animal Science 60, 55–64. open url image1

Stice FL, Keefer SL (1993) Multiple generational bovine embryo cloning. Biology of Reproduction 48, 715–719.
PubMed |
open url image1

Stice SL, Robl JM, Ponce de Leon FA, Jerry J, Golueke PG, Cibelli JB, Kane JJ (1998) Cloning: new breakthroughs leading to commercial opportunities. Theriogenology 49, 129–138.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Vajta G, Booth PJ, Holm P, Greve T, Callesen H (1997) Successful vitrification of early stage bovine in vitro produced embryos with the open pulled straw (OPS) method. Cryo Letters 18, 191–195. open url image1

Vajta G, Holm P, Kuwayama M, Booth P, Jacobsen H, Greve T, Callesen H (1998) Open pulled straw (OPS) vitrification: a new way to reduce cryoinjuries of bovine ova and embryos. Molecular Reproduction and Development 51, 53–58.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Vajta G, Lewis IM, Hytell P, Thouas G, Trounson A (2001) Somatic cell cloning without micromanipulators. Cloning 3, 89–93.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Vajta G, Lewis IM, Trounson AO, Purup S, Maddox-Hyttel P, Schmidt M, Pedersen HG, Greve T, Callesen H (2003) Hand-made somatic cell cloning in cattle: analysis of factors contributing to the high efficiency in vitro. Biology of Reproduction 68, 571–578.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Wagtendonk-de Leeuw van AM, Den Daas JHG, Kruip TAM, Rall WF (1995) Comparison of efficacy of conventional slow freezing and rapid cryopreservation methods for bovine embryos. Cryobiology 32, 157–167.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Wagtendonk-de Leeuw van AM, Mullart E, de Roos APW, Merton JS, den Daas JHG, Kemp B, de Ruigh L (2000) Effects of different reproduction techniques: AI, MOET or IVP, on health and welfare of bovine offspring. Theriogenology 53, 575–597.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Walker SK, Heard TM, Seamark RF (1992) In vitro culture of sheep embryos without co-culture: successes and perspectives. Theriogenology 37, 111–126.
Crossref | GoogleScholarGoogle Scholar | open url image1

Wells DN, Laible G, Tucker FC, Miller AL, Oliver JE , et al. (2003) Coordination between donor cell type and cell cycle stage improves nuclear cloning efficiency in cattle. Theriogenology 59, 45–59.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Wells DN, Misica PM, Tervit HR (1999) Production of cloned calves following nuclear transfer with cultured adult mural granulosa cells. Biology of Reproduction 60, 996–1005.
PubMed |
open url image1

Willadsen SM (1986) Nuclear transplantation in sheep embryos. Nature 320, 63–65.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Willadsen SM, Jansen RE, McAllister RJ, Shea BF, Hamilton G, McDermand D (1991) The viability of late morula and blastocysts produced by nuclear transplantation in cattle. Theriogenology 35, 161–170.
Crossref | GoogleScholarGoogle Scholar | open url image1

Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810–813.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Wilson JM, Williams JD, Bondioli KR, Looney CR, Westhusin ME, McCalla DF (1995) Comparison of birth weight and growth characteristics of bovine calves produced by nuclear transfer (cloning), embryo transfer and natural mating. Animal Reproduction Science 38, 73–83.
Crossref | GoogleScholarGoogle Scholar | open url image1

Young LE, Sinclair KD, Wilmut I (1998) Large offspring syndrome in cattle and sheep. Reviews of Reproduction 3, 155–163.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Ziomek CA (1998) Commercialization of proteins produced in the mammary gland. Theriogenology 49, 139–144.
Crossref | GoogleScholarGoogle Scholar | PubMed | open url image1

Zuelke KA (1998) Transgenic modification of cows milk for value-added processing. Reproduction, Fertility and Development 10, 671–676.
Crossref | GoogleScholarGoogle Scholar | open url image1