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Genetically engineering milk

Published online by Cambridge University Press:  12 February 2016

C. Bruce A. Whitelaw*
Affiliation:
The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
Akshay Joshi
Affiliation:
The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
Satish Kumar
Affiliation:
Centre for Cellular and Molecular Biology, Hyderabad, India
Simon G. Lillico
Affiliation:
The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
Chris Proudfoot
Affiliation:
The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
*
*For correspondence; e-mail: bruce.whitelaw@roslin.ed.ac.uk

Abstract

It has been thirty years since the first genetically engineered animal with altered milk composition was reported. During the intervening years, the world population has increased from 5bn to 7bn people. An increasing demand for protein in the human diet has followed this population expansion, putting huge stress on the food supply chain. Many solutions to the grand challenge of food security for all have been proposed and are currently under investigation and study. Amongst these, genetics still has an important role to play, aiming to continually enable the selection of livestock with enhanced traits. Part of the geneticist's tool box is the technology of genetic engineering. In this Invited Review, we indicate that this technology has come a long way, we focus on the genetic engineering of dairy animals and we argue that the new strategies for precision breeding demand proper evaluation as to how they could contribute to the essential increases in agricultural productivity our society must achieve.

Type
Research Article
Copyright
Copyright © Proprietors of Journal of Dairy Research 2016 

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References

Anon, 2009 Recombinant human Antithrombin (ATryn). Medical Letter on Drugs and Therapeutics 51 8384Google Scholar
Bleck, GT, White, BR, Miller, DJ & Wheeler, MB 1998 Production of bovine alpha-lactalbumin in the milk of transgenic pigs. Journal of Animal Science 76 30723078CrossRefGoogle ScholarPubMed
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. Nature Biotechnology 21 157162CrossRefGoogle ScholarPubMed
Caroli, AM, Chessa, S & Erhardt, GJ 2009 Invited review: milk protein polymorphisms in cattle: effect on animal breeding and human nutrition. Journal of Dairy Science 92 53355352CrossRefGoogle ScholarPubMed
Clark, J & Whitelaw, B 2003 A future for transgenic livestock. Nature Reviews Genetics 4 825833CrossRefGoogle ScholarPubMed
Clark, AJ, Ali, S, Archibald, AL, Bessos, H, Brown, P, Harris, S, McClenaghan, M, Prowse, C, Simons, JP, Whitelaw, CB & Wilmut, I 1989 The molecular manipulation of milk composition. Genome 31 950955CrossRefGoogle ScholarPubMed
Clop, A, Vidal, O & Amills, M 2012 Copy number variation in the genomes of domestic animals. Animal Genetics 43 503517CrossRefGoogle ScholarPubMed
Cong, L, Ran, FA, Cox, D, Lin, S, Barretto, R, Habib, N, Hsu, PD, Wu, X, Jiang, W, Marraffini, LA & Zhang, F 2013 Multiplex genome engineering using CRISPR/Cas systems. Science 339 819823CrossRefGoogle ScholarPubMed
Cooper, CA, Nelson, KM, Maga, EA & Murray, JD 2013 Consumption of transgenic cows’ milk containing human lactoferrin results in beneficial changes in the gastrointestinal tract and systemic health of young pigs. Transgenic Research 22 571578CrossRefGoogle ScholarPubMed
Cooper, CA, Maga, EA & Murray, JD 2014 Consumption of transgenic milk containing the antimicrobials lactoferrin and lysozyme separately and in conjunction by 6-week-old pigs improves intestinal and systemic health. Journal of Dairy Research 81 3037CrossRefGoogle ScholarPubMed
Cooper, CA, Maga, EA & Murray, JD 2015 Production of human lactoferrin and lysozyme in the milk of transgenic dairy animals: past, present, and future. Transgenic Research 24 605614CrossRefGoogle ScholarPubMed
Crispo, M, Mulet, AP, Tesson, L, Barrera, N, Cuadro, F, dos Santos-Neto, PC, Nguyen, TH, Creneguy, A, Brusselle, L, Anegon, I & Menchaca, A 2015 Efficient generation of Myostatin knock-out sheep using CRISPR/Cas9 technology and microinjection into zygotes. PLoS One 10 e0136690CrossRefGoogle ScholarPubMed
Cui, C, Song, Y, Liu, J, Ge, H, Li, Q, Huang, H, Hu, L, Zhu, H, Jin, Y & Zhang, Y 2015 Gene targeting by TALEN-induced homologous recombination in goats directs production of beta-lactoglobulin-free, high-human lactoferrin milk. Scientific Reports 5 10482CrossRefGoogle ScholarPubMed
Desai, N, Antonopoulos, D, Gilbert, JA, Glass, EM & Meyer, F 2012 From genomics to metagenomics. Current Opinions in Biotechnology 23 7276CrossRefGoogle ScholarPubMed
Enjapoori, AK, Grant, TR, Nicol, SC, Lefevre, CM, Nicholas, KR & Sharp, JA 2014 Monotreme lactation protein is highly expressed in monotreme milk and provides antimicrobial protection. Genome Biology and Evolution 6 27542773CrossRefGoogle ScholarPubMed
Fahrenkrug, SC, Blake, A, Carlson, DF, Doran, T, Van Eenennaam, A, Faber, D, Galli, C, Gao, Q, Hackett, PB, Li, N, Maga, EA, Muir, WM, Murray, JD, Shi, D, Stotish, R, Sullivan, E, Taylor, JF, Walton, M, Wheeler, M, Whitelaw, B & Glenn, BP 2010 Precision genetics for complex objectives in animal agriculture. Journal of Animal Science 88 25302539CrossRefGoogle ScholarPubMed
Hammer, RE, Pursel, VG, Rexroad, CE Jr, Wall, RJ, Bolt, DJ, Ebert, KM, Palmiter, RD & Brinster, RL 1985 Production of transgenic rabbits, sheep and pigs by microinjection. Nature 315 680683CrossRefGoogle ScholarPubMed
Houdebine, LM 2000 Transgenic animal bioreactors. Transgenic Research 9 305320CrossRefGoogle ScholarPubMed
Huber, RC, Kolb, AF, Lillico, S, Carlisle, A, Sandoe, P, Sorensen, DB, Remuge, L, Whitelaw, BC & Olsson, AI 2013 Behaviour of postnatally growth-impaired mice during malnutrition and after partial weight recovery. Nutritional Neuroscience 16 125134CrossRefGoogle ScholarPubMed
Jabed, A, Wagner, S, McCracken, J, Wells, DN & Laible, G 2012 Targeted microRNA expression in dairy cattle directs production of beta-lactoglobulin-free, high-casein milk. Proceedings of the National Academy of Sciences of the USA 109 1681116816CrossRefGoogle ScholarPubMed
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. Nature Biotechnology 17 160164CrossRefGoogle ScholarPubMed
Kind, A & Schnieke, A 2008 Animal pharming, two decades on. Transgenic Research 17 10251033CrossRefGoogle Scholar
Kolb, AF, Webster, J, Whitelaw, CB & Siddell, SG 2001 A virus-neutralising monoclonal antibody expressed in the milk of transgenic mice. Advances in Experimental Medicine and Biology 494 411414CrossRefGoogle ScholarPubMed
Kolb, AF, Huber, RC, Lillico, SG, Carlisle, A, Robinson, CJ, Neil, C, Petrie, L, Sorensen, DB, Olsson, IA & Whitelaw, CB 2011 Milk lacking alpha-casein leads to permanent reduction in body size in mice. PLoS ONE 6 e21775CrossRefGoogle ScholarPubMed
Kumar, S, Clarke, AR, Hooper, ML, Horne, DS, Law, AJ, Leaver, J, Springbett, A, Stevenson, E & Simons, JP 1994 Milk composition and lactation of beta-casein-deficient mice. Proceedings of the National Academy of Sciences of the USA 91 61386142CrossRefGoogle ScholarPubMed
Lanphier, E, Urnov, F, Haecker, SE, Werner, M & Smolenski, J 2015 Don't edit the human germ line. Nature 519 410411CrossRefGoogle ScholarPubMed
Lillico, SG, Proudfoot, C, Carlson, DF, Stverakova, D, Neil, C, Blain, C, King, TJ, Ritchie, WA, Tan, W, Mileham, AJ, McLaren, DG, Fahrenkrug, SC & Whitelaw, CB 2013 Live pigs produced from genome edited zygotes. Scientific Reports 3 2847CrossRefGoogle ScholarPubMed
Liu, X, Ping, H & Zhang, C 2014a Rapid establishment of a HEK 293 cell line expressing FVIII-BDD using AAV site-specific integration plasmids. BMC Research Notes 7 626CrossRefGoogle Scholar
Liu, X, Wang, Y, Tian, Y, Yu, Y, Gao, M, Hu, G, Su, F, Pan, S, Luo, Y, Guo, Z, Quan, F & Zhang, Y 2014b Generation of mastitis resistance in cows by targeting human lysozyme gene to beta-casein locus using zinc-finger nucleases. Proceedings of the Royal Society B: Biological Sciences 281 20133368CrossRefGoogle Scholar
Lubon, H, Paleyanda, RK, Velander, WH & Drohan, WN 1996 Blood proteins from transgenic animal bioreactors. Transfusion Medicine Reviews 10 131143CrossRefGoogle ScholarPubMed
Maga, EA, Cullor, JS, Smith, W, Anderson, GB & Murray, JD 2006 Human lysozyme expressed in the mammary gland of transgenic dairy goats can inhibit the growth of bacteria that cause mastitis and the cold-spoilage of milk. Foodborne Pathogens and Disease 3 384392CrossRefGoogle ScholarPubMed
Marshall, KM, Hurley, WL, Shanks, RD & Wheeler, MB 2006 Effects of suckling intensity on milk yield and piglet growth from lactation-enhanced gilts. Journal of Animal Science 84 23462351CrossRefGoogle ScholarPubMed
Mathews, DJ, Chan, S, Donovan, PJ, Douglas, T, Gyngell, C, Harris, J, Regenberg, A & Lovell-Badge, R 2015 CRISPR: a path through the thicket. Nature 527 159161CrossRefGoogle ScholarPubMed
McClenaghan, M, Springbett, A, Wallace, RM, Wilde, CJ & Clark, AJ 1995 Secretory proteins compete for production in the mammary gland of transgenic mice. Biochemal Journal 310 637641CrossRefGoogle ScholarPubMed
Murray, JD & Maga, EA 2010 Is there a risk from not using GE animals? Transgenic Research 19 357361CrossRefGoogle Scholar
Ni, W, Qiao, J, Hu, S, Zhao, X, Regouski, M, Yang, M, Polejaeva, IA & Chen, C 2014 Efficient gene knockout in goats using CRISPR/Cas9 system. PLoS One 9 e106718CrossRefGoogle ScholarPubMed
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. Journal of Animal Science 80 10901096CrossRefGoogle ScholarPubMed
Nongonierma, AB & FitzGerald, RJ 2015 Bioactive properties of milk proteins in humans: a review. Peptides 73 2034CrossRefGoogle ScholarPubMed
Palmiter, RD & Brinster, RL 1986 Germ-line transformation of mice. Annual Review of Genetics 20 465499CrossRefGoogle Scholar
Peng, J, Wang, Y, Jiang, J, Zhou, X, Song, L, Wang, L, Ding, C, Qin, J, Liu, L, Wang, W, Liu, J, Huang, X, Wei, H & Zhang, P 2015 Production of human albumin in pigs through CRISPR/Cas9-mediated Knockin of human cDNA into swine albumin locus in the Zygotes. Scientific Reports 5 16705CrossRefGoogle ScholarPubMed
Pollock, DP, Kutzko, JP, Birck-Wilson, E, Williams, JL, Echelard, Y & Meade, HM 1999 Transgenic milk as a method for the production of recombinant antibodies. Journal of Immunological Methods 231 147157CrossRefGoogle ScholarPubMed
Proudfoot, C, Carlson, DF, Huddart, R, Long, CR, Pryor, JH, King, TJ, Lillico, SG, Mileham, AJ, McLaren, DG, Whitelaw, CB & Fahrenkrug, SC 2015 Genome edited sheep and cattle. Transgenic Research 24 147153CrossRefGoogle ScholarPubMed
Pursel, VG, Pinkert, CA, Miller, KF, Bolt, DJ, Campbell, RG, Palmiter, RD, Brinster, RL & Hammer, RE 1989 Genetic engineering of livestock. Science 244 12811288CrossRefGoogle ScholarPubMed
Pursel, VG, Bolt, DJ, Miller, KF, Pinkert, CA, Hammer, RE, Palmiter, RD & Brinster, RL 1990 Expression and performance in transgenic pigs. Journal of Reproduction and Fertility Supplement 40 235–45Google ScholarPubMed
Pursel, VG, Mitchell, AD, Bee, G, Elsasser, TH, McMurtry, JP, Wall, RJ, Coleman, ME & Schwartz, RJ 2004 Growth and tissue accretion rates of swine expressing an insulin-like growth factor I transgene. Animal Biotechnology 15 3345CrossRefGoogle ScholarPubMed
Qian, L, Tang, M, Yang, J, Wang, Q, Cai, C, Jiang, S, Li, H, Jiang, K, Gao, P, Ma, D, Chen, Y, An, X, Li, K & Cui, W 2015 Targeted mutations in myostatin by zinc-finger nucleases result in double-muscled phenotype in Meishan pigs. Scientific Reports 5 14435CrossRefGoogle ScholarPubMed
Reh, WA, Maga, EA, Collette, NM, Moyer, A, Conrad-Brink, JS, Taylor, SJ, DePeters, EJ, Oppenheim, S, Rowe, JD, BonDurant, RH, Anderson, GB & Murray, JD 2004 Hot topic: using a stearoyl-CoA desaturase transgene to alter milk fatty acid composition. Journal of Dairy Science 87 35103514CrossRefGoogle ScholarPubMed
Rijnkels, M, Elnitski, L, Miller, W & Rosen, JM 2003 Multispecies comparative analysis of a mammalian-specific genomic domain encoding secretory proteins. Genomics 82 417432CrossRefGoogle ScholarPubMed
Schaeffer, SM & Nakata, PA 2015 CRISPR/Cas9-mediated genome editing and gene replacement in plants: transitioning from lab to field. Plant Science 240 130142CrossRefGoogle ScholarPubMed
Schnieke, AE, Kind, AJ, Ritchie, WA, Mycock, K, Scott, AR, Ritchie, M, Wilmut, I, Colman, A & Campbell, KH 1997 Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278 21302133CrossRefGoogle ScholarPubMed
Shekar, PC, Goel, S, Rani, SD, Sarathi, DP, Alex, JL, Singh, S & Kumar, S 2006 kappa-casein-deficient mice fail to lactate. Proceedings of the National Academy of Sciences of the USA 103 80008005CrossRefGoogle Scholar
Simons, JP, McClenaghan, M & Clark, AJ 1987 Alteration of the quality of milk by expression of sheep beta-lactoglobulin in transgenic mice. Nature 328 530532CrossRefGoogle ScholarPubMed
Sola, I, Castilla, J, Pintado, B, Sanchez-Morgado, JM, Whitelaw, CB, Clark, AJ & Enjuanes, L 1998 Transgenic mice secreting coronavirus neutralizing antibodies into the milk. Journal of Virology 72 37623772Google ScholarPubMed
Stacey, A, Schnieke, A, Kerr, M, Scott, A, McKee, C, Cottingham, I, Binas, B, Wilde, C & Colman, A 1995 Lactation is disrupted by alpha-lactalbumin deficiency and can be restored by human alpha-lactalbumin gene replacement in mice. Proceedings of the National Academy of Sciences of the USA 92 28352839CrossRefGoogle ScholarPubMed
Tan, W, Carlson, DF, Lancto, CA, Garbe, JR, Webster, DA, Hackett, PB & Fahrenkrug, SC 2013 Efficient nonmeiotic allele introgression in livestock using custom endonucleases. Proceedings of the National Academy of Sciences of the USA 110 1652616531CrossRefGoogle ScholarPubMed
Wall, RJ, Pursel, VG, Shamay, A, McKnight, RA, Pittius, CW & Hennighausen, L 1991 High-level synthesis of a heterologous milk protein in the mammary glands of transgenic swine. Proceedings of the National Academy of Sciences of the USA 88 16961700CrossRefGoogle ScholarPubMed
Wall, RJ, Powell, AM, Paape, MJ, Kerr, DE, Bannerman, DD, Pursel, VG, Wells, KD, Talbot, N & Hawk, HW 2005 Genetically enhanced cows resist intramammary Staphylococcus aureus infection. Nature Biotechnology 23 445451CrossRefGoogle ScholarPubMed
Wei, J, Wagner, S, Lu, D, Maclean, P, Carlson, DF, Fahrenkrug, SC & Laible, G 2015 Efficient introgression of allelic variants by embryo-mediated editing of the bovine genome. Scientific Reports 5 11735CrossRefGoogle ScholarPubMed
Whitelaw, B 1999 Toward designer milk. Nature Biotechnology 17 135136CrossRefGoogle ScholarPubMed
Wilmut, I & Whitelaw, CB 1994 Strategies for production of pharmaceutical proteins in milk. Reproduction, Fertility and Development 6 625630CrossRefGoogle ScholarPubMed
Wu, H, Wang, Y, Zhang, Y, Yang, M, Lv, J, Liu, J & Zhang, Y 2015 TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis. Proceedings of the National Academy of Sciences of the USA 112 E1530E1539CrossRefGoogle ScholarPubMed
Yang, H, Wang, H, Shivalila, CS, Cheng, AW, Shi, L & Jaenisch, R 2013 One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering. Cell 154 13701379CrossRefGoogle ScholarPubMed
Zhao, J, Xu, W, Ross, JW, Walters, EM, Butler, SP, Whyte, JJ, Kelso, L, Fatemi, M, Vanderslice, NC, Giroux, K, Spate, LD, Samuel, MS, Murphy, CN, Wells, KD, Masiello, NC, Prather, RS & Velander, WH 2015 Engineering protein processing of the mammary gland to produce abundant hemophilia B therapy in milk. Scientific Reports 5 14176CrossRefGoogle ScholarPubMed
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