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Abstract Abstract Transgenic animal as bioreactors is a novel expression system capable of producing foreign proteins in live animal tissues and body fluids at an industrial scale level, such as the milk, blood, urine, seminal plasma and egg white. The use of the transgenic animal as bioreactors offers attractive advantages, residing on the low production costs allied to high productivity and quality and easy purification of the recombinant proteins. Since recombinant human antithrombin Ⅲ (ATryn), purified from the milk of transgenic goats (Capra hircus), was first approved by the European Medicines Agency (EMA) for marketing in European Union countries on February 6, 2009, this novel protein production system revolutionized the landscape of scientific and marketing possibilities of biopharmaceutical. Human lysozyme (hLZ), as a natural non-specific immune protein, is an important component of human breast milk. It hydrolyzes the glycosidic β-(1-4) linkage between Nacetylmuramic acid and N-acetylglucosamine of the peptidoglycan polymer in the bacterial cell wall and plays an important role in killing bacteria, modulating the inflammatory response, influencing the composition of intestinal microbiota populations. Compared to hen egg white lysozyme, hLZ is a safe and non-allergenic protein, which has more lytic activity. hLZ could be widely used in food preservation, infant milk powder, antibacterial anti-inflammatory drugs and antibiotic substitution. However, its commercial use is very limited due to the poor source of human breast milk. In this paper, we firstly summarized the progresses of recombinant human lysozyem expressed in the milk of transgenic mouse, cows, goats and pigs, and in the egg whites of transgenic hens. Then we talked about the physicochemical properties, purification process and biological function of recombinant human lysozyme, and biosafety evaluation of transgenic animals. Finally, we analyzed the existing problems and the future development of the industrialization of human lysozyme transgenic animal. Overall, the review aimed at providing better understanding of hLZ transgenic animal and industrialization to researchers.
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Received: 31 October 2016
Published: 31 March 2017
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[1]Brundige, D. R., E. A. Maga, K. C. Klasing, et al..Lysozyme transgenic goats' milk influences gastrointestinal morphology in young pigs[J].The Journal of Nutrition, 2008, 138(5):921-926[2]Brundige, D. R., E. A. Maga, K. C. Klasing, et al..Consumption of pasteurized human lysozyme transgenic goats' milk alters serum metabolite profile in young pigs[J].Transgenic Res, 2010, 19(4):563-574[3]Cao, D., H. Wu, Q. Li, et al..Expression of recombinant human lysozyme in egg whites of transgenic hens[J].PLoS One, 2015, 10(2):e118626-15[4]Carvalho, E. B., E. A. Maga, J. S. Quetz, et al..Goat milk with and without increased concentrations of lysozyme improves repair of intestinal cell damage induced by enteroaggregative Escherichia coli[J].BMC Gastroenterol, 2012, 12(106):1-9[5]Cooper, C. A., D. R. Brundige, W. A. Reh, et al..Lysozyme transgenic goats' milk positively impacts intestinal cytokine expression and morphology[J].Transgenic Res, 2011, 20(6):1235-1243[6]Cooper, C.A., E. A. Maga, and J. D. Murray, .Production of human lactoferrin and lysozyme in the milk of transgenic dairy animals: past, present, and future[J].Transgenic Res, 2015, 24(4):605-614[7]Cooper, C.A., K. L. Garas, E. A. Maga, et al..Consuming transgenic goats' milk containing the antimicrobial protein lysozyme helps resolve diarrhea in young pigs[J].PLoS One, 2013, 8(3):e58409-8[8]Ginsburg, I.Role of lipoteichoic acid in infection and inflammation[J].Lancet Infect Dis, 2002, 2(3):171-179[9]Gordon, L. I.; Douglas, S. D.; Kay, N. E, et al..Modulation of neutrophil function by lysozyme. Potential negative feedback system of inflammation[J].J Clin Invest, 1979, 64(1):226-232[10]Jackson, K. A., J. M. Berg, J. D. Murray, et al..Evaluating the fitness of human lysozyme transgenic dairy goats: growth and reproductive traits[J].ransgenic Res, 2010, 19(6):977-986[11]Liu, J., Y. Luo, L. Zheng, et al..Establishment and characterization of fetal fibroblast cell lines for generating human lysozyme transgenic goats by somatic cell nuclear transfer[J].Transgenic Res, 2013, 22(5):893-903[12]Liu, S, X. Li, D. Lu, et al..High-level expression of bioactive recombinant human lysozyme in the milk of transgenic mice using a modified human lactoferrin BAC[J].Transgenic Res, 2012, 21(2):407-414[13]Liu, X, Y. Wang, Y. Tian, et al..Generation of mastitis resistance in cows by targeting human lysozyme gene to beta-casein locus using zinc-finger nucleases[J].Proc Biol Sci, 2014, 281(1780):20133368-10[14]Lu, D, Q. Li, Z. Wu, et al..High-level recombinant human lysozyme expressed in milk of transgenic pigs can inhibit the growth of Escherichia coli in the duodenum and influence intestinal morphology of sucking pigs.[J].PLoS One, 2014, 9(2):e89130-9[15]Lu, D, S. Liu, F. Ding, et al..Large-scale production of functional human lysozyme from marker-free transgenic cloned cows[J].Sci Rep, v. 6, p. 22947., 2016, 6(22947):1-9[16]Lu, D, S. Liu, S. Shang, et al..Production of transgenic-cloned pigs expressing large quantities of recombinant human lysozyme in milk[J].PLoS One, 2015, 10(5):e123551-14[18]Maga, E.A., C. F. Shoemaker, J. D. Rowe, et al..Production and processing of milk from transgenic goats expressing human lysozyme in the mammary gland[J].J Dairy Sci, 2006, 89(2):518-524[19]Maga, E.A., G. B. Anderson, M. C. Huang, et al..Expression of human lysozyme mRNA in the mammary gland of transgenic mice[J].Transgenic Res, 1994, 3(1):36-42[20]Maga, E.A., G. B. Anderson, and J. D. Murray,.The effect of mammary gland expression of human lysozyme on the properties of milk from transgenic mice[J].J Dairy Sci, 1995, 78(2):2645-2652[21]Maga, E.A., J. S. Cullor, W. Smith, et al..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[J].Foodborne Pathog Dis, 2006, 3(4):384-392[22]Maga, E.A., P. T. Desai, B. C. Weimer, et al..Consumption of lysozyme-rich milk can alter microbial fecal populations[J].Appl Environ Microbiol,, 2012, 78(17):6153-6160[23]Maga, E.A., R. L. Walker, G. B. Anderson,.Consumption of milk from transgenic goats expressing human lysozyme in the mammary gland results in the modulation of intestinal microflora[J].Transgenic Res, 2006, 15(4):515-519[24]Montagne, P, M. L. Cuilliere, C. Mole, et al..Changes in lactoferrin and lysozyme levels in human milk during the first twelve weeks of lactation[J].Adv Exp Med Biol, 2001, 501(0):241-247[25]Ohno, N, and D. C. Morrison,.Lipopolysaccharide interactions with lysozyme differentially affect lipopolysaccharide immunostimulatory activity[J].Eur J Biochem, 1989, 186(3):629-636[26]Scharfen, E.C., D. A. Mills, and E. A. Maga, .Use of human lysozyme transgenic goat milk in cheese making: effects on lactic acid bacteria performance[J].J Dairy Sci, 2007, 90(9):4084-4091[27]Tong, J, H. Wei, X. Liu, et al..Production of recombinant human lysozyme in the milk of transgenic pigs[J].Transgenic Res, 2011, 20(2):417-419[28]Wilken, L.R., and Z. L. Nikolov,.Process evaluations and economic analyses of recombinant human lysozyme and hen egg-white lysozyme purifications[J].Biotechnol Prog, 2011, 27(3):733-743[29]Wu, H, D. Cao, T. Liu, et al..Purification and Characterization of Recombinant Human Lysozyme from Eggs of Transgenic Chickens[J].PLoS One, 2015, 10(12):e146032-17[30]Wu, X, Y. Lin, Y. Xi,.The development of transgenic mice for the expression of large amounts of human lysozyme in milk[J].Biotechnol Lett, 2014, 36(6):1197-1202[31]Yang, B, J. Wang, B. Tang, et al..Characterization of bioactive recombinant human lysozyme expressed in milk of cloned transgenic cattle[J].PLoS One, 2011, 6(3):e17593-10[32]Yu, H, J. Chen, S. Liu, et al..Large-Scale Production of Functional Human Lysozyme in Transgenic Cloned Goats[J].Journal of Biotechnology, 2013, 168(0):676-683[33]Yu, Z, Q. Meng, H. Yu, et al..Expression and bioactivity of recombinant human lysozyme in the milk of transgenic mice[J].J Dairy Sci, 2006, 89(8):2911-2918[34]Zhang, R, C. Guo, S. Sui, et al..Comprehensive assessment of milk composition in transgenic cloned cattle[J].PLoS One, 2012, 7(11):e49697-16[35]Zhao, J, J. Xu, J. Wang, et al..Impacts of human lysozyme transgene on the microflora of pig feces and the surrounding soil[J].J Biotechnol, 2012, 16(4):437-444 |
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