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Expression of the Transgene is Consistently Inherited to High Numbers of Generations and Independent on Its Source  

Zheng, Zhen-Yu (The College of Animal Husbandry and Veterinary, Henan Agricultural University)
Oh, Keon-Bong (Center for Regenerative Medicine, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Koo, Deog-Bon (Center for Regenerative Medicine, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Han, Yong-Mahn (Department of Biological Sciences, Korea Advanced Institute of Science and Technology)
Lee, Kyung-Kwang (Center for Regenerative Medicine, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
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Abstract
Most studies on transgenic bioreactors have focused on expression levels of interest genes. In this study we examined whether transgenic bioreactors would inherit expression level of the Oansgene to long-term generations independently of transgene sources. We employed three transgenic mice, which were separately reported, carrying different transgenes and copy numbers, 27 kb of hLF and 22 kb of hIL-10 genomic sequences, and 1.3 kb of hTPO cDNA, respectively. Three females of the transgenic lineages crossbred with a wild-type male up to 20 generations to test transgenic frequencies of their progenies and to determine expression levels of the transgenes. Ultimately, transmission rates of kLF, hIL-10, and hTPO were $64.3{\pm}7.0$, $59.3{\pm}9.8$, and $56.1{\pm}9.7$, respectively, appeared following Mendelian pattern of inheritance. Notably, we found that levels of expressions of hLF, hIL-10, and hTPO in milk were sustained to high numbers of generations. No transgene silencing of expression was observed in every generations of all transgenic mice. In conclusion, we suggest that once established animal bioreactors could consistently transmit the transgene to continual generations, without loss of expressional activity, independently of transgene sources.
Keywords
Human lactoferrin; Human TPO; Human IL-10; Transmission;
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1 Choi YH, Oh KB, Kang YK, Fang NS, Seo KW, Lee KK, Lee CS (1998): Stable inheritance of bovine bcasein/bovine growth hormone fusion gene in transgenic mice. Korean J Animal Reprod 22(3):237-244
2 Rudolph NS (1999): Biopharmaceutical production in transgenic livestock. Trends Biotechnol 17(9):367-374   DOI   ScienceOn
3 Sohn BH, Kim SJ, Park H, Park SK, Lee SC, Hong HJ, Park YS, Lee KK (1999): Expression and characterization of bioactive human thrombopoietin in the milk of transgenic mice. DNA and Cell Biology 18(11):845-852   DOI   ScienceOn
4 Wu B, Sun YH, Wang YW, Wang YP, Zhu ZY (2005): Characterization of transgene integration pattern in F4 hGH-transgenic common carp (Cyprinus carpio L.). Cell Res 15(6):447-454   DOI   ScienceOn
5 Markaki M, Drabek D, Livadaras I, Craig RK, Grosveld F, Savakis C (2007): Stable expression of human growth hormone over 50 generations in transgenic insect larvae. Transgenic Research 16(1):99-107   DOI   ScienceOn
6 Sohn BH, Chang HG, Kang HS, Yoon H, Bae YS, Lee KK, Kim SJ (2003): High level expression of the bioactive human interleukin-10 in milk of transgenic mice. J Biotechnol 103(1):11-19   DOI   ScienceOn
7 Ko JH, Lee CS, Kim KH, Pang MG, Koo JS, Fang N, Koo DB, Oh KB, Youn WS, Zheng GD, Park JS, Kim SJ, Han YM, Choi IY, Lim J, Shin ST, Jin SW, Lee KK, Yoo OJ (2000): Production of biologically active human granulocyte colony stimulating factor in the milk of transgenic goat. Transgenic Research 9(3):215-222   DOI   ScienceOn
8 Dobie KW, Lee M, Fantes JA, Graham E, Clark AJ, Springbett A, Lathe R, McClenaghan M (1996): Variegated transgene expression in mouse mammary gland is determined by the transgene integration locus. Proceedings of the National Academy of Sciences of the United States of America 93(13):6659-6664
9 Lee CS, Kim K, Yu DY, Lee KK (1996): An efficient expression of human growth hormone (hGH) in the milk of transgenic mice using rat beta-casein/hGH fusion genes. Appl Biochem Biotechnol 56(3):211-222   DOI   ScienceOn
10 Houdebine LM (2000): Transgenic animal bioreactors. Transgenic Research 9(4-5):305-320   DOI   ScienceOn
11 Gordon K, Lee E, Vitale JA, Smith AE, Westphal H, Hennighausen L (1992): Production of human tissue plasminogen activator in transgenic mouse milk. 1987. Biotechnology 24:425-428
12 Lee WK, Kim SJ, Hong S, Lee T, Han Y, Yoo OJ, Im KS, KL (1998): Expression of a bovine b-casein/human lysozyme fusion gene in the mammary gland of transgenic mice. J Biochem Mol Biol 31:413-417
13 Kim SJ, Lee KW, Yu DY, Han YM, Lee CS, Nam MS, Moon HB, Lee KK (1997): Expression analysis of a bovine $\beta$-casein/Human lactoferrin hybrid gene in transgenic mice. Journal of Reproduction and Development 43(2):143-149   DOI   ScienceOn
14 Opsahl ML, Springbett A, Lathe R, Colman A, Mc-Clenaghan M, Whitelaw CB (2003): Mono-allelic expression of variegating transgene locus in the mouse. Transgenic Research 12(6):661-669   DOI   ScienceOn
15 Kim SJ, Sohn BH, Jeong S, Pak KW, Park JS, Park IY, Lee TH, Choi YH, Lee CS, Han YM, Yu DY, Lee KK (1999): High-level expression of human lactoferrin in milk of transgenic mice using genomic lactoferrin sequence. J Biochem 126(2):320-325   DOI
16 Aigner B, Fleischmann M, Muller M, Brem G (1999): Stable long-term germ-line transmission of transgene integration sites in mice. Transgenic Research 8(1):1-8   DOI   ScienceOn
17 Han YM, Koo DB, Park JS, Kim YH, Lee KJ, Lee KK (2005): Transmission of bovine $\beta$-casein/human lactoferrin fusion gene in transgenic cattle. Reprod Dev Biol 29(4):235-239   과학기술학회마을
18 Lee CS, Fang NZ, Koo DB, Lee YS, Zheng GD, Oh KB, Youn WS, Han YM, Kim SJ, Lim JH, Shin ST, Jin SW, Lee KS, Ko JH, Koo JS, Park CS, Yoo OJ, Lee KK (2000): Embryo recovery and transfer for the production of transgenic goats from Korean native strain, Capra hircus aegagrus. Small Rumin Res 37(1-2): 57-63   DOI
19 Dobie K, Mehtali M, McClenaghan M, Lathe R (1997): Variegated gene expression in mice. Trends Genet 13(4):127-130   DOI   ScienceOn
20 Zheng ZY, Koo DB, Han YM, Lee KK (2004): Stable transmission and continuous expression of human interleukin-10 transgene in the offspring of transgenic mice. Reprod Dev Biol 28(3):203-207
21 Zheng ZY, Oh KB, Han YM, Lee KK (2003): Stable transmission and expression of TPO transgene up to 10 generation in the transgenic mice. Korean J Animal Reprod 27(1):9-14
22 Migliaccio AR, Bengra C, Ling J, Pi W, Li C, Zeng S, Keskintepe M, Whitney B, Sanchez M, Migliaccio G, Tuan D (2000): Stable and unstable transgene integration sites in the human genome: extinction of the Green Fluorescent Protein transgene in K562 cells. Gene 256(1-2):197-214   DOI
23 Oh KB, Choi YH, Kang YK, Choi WS, Kim MO, Lee KS, Lee KK, Lee CS (1999): A hybrid bovine betacasein/bGH gene directs transgene expression to the lung and mammary gland of transgenic mice. Transgenic Research 8(4):307-311   DOI   ScienceOn