摘要
制备“乳腺生物反应器”生产药用蛋白或生产“人源化”羊奶或牛奶是近年来转基因研究的热点。基因打靶技术不仅可以实现对基因组中特定基因的敲除，从根本上阻断目的基因的表达；而且可以将外源目的基因定位整合到基因组的特定位点，借助细胞内源性调控序列指导外源目的基因高效表达，从而有效降低随机整合带来的位置效应的影响。α-乳白蛋白（α-lactalbumin，ALA）是人乳中主要的乳清蛋白，富含色氨酸、赖氨酸及半胱氨酸等必需氨基酸，近年的研究发现其在预防新生儿胃肠道感染等方面有重要作用。而作为山羊乳中主要的乳清蛋白，β-乳球蛋白（β-lactoglobulin，BLG）在人乳中并不存在，因而可能和牛乳中BLG一样是引起婴幼儿乳过敏症的一种重要的过敏原。因此，本研究通过基因打靶的手段，将BLG基因敲除或用hALA基因置换BLG基因CDS区，以期为生产“人源化”山羊乳奠定基础。
1.以人血液基因组DNA为模板，通过PCR成功克隆获得人乳白蛋白（hALA）基因；构建了hALA基因的真核表达载体，将其转染到293T细胞中作为人乳腺上皮细胞的替代细胞，通过RT-PCR的方法成功克隆得到hALA cDNA。这一方法为克隆组织材料难以采集的cDNA提供了一种有效的备选方案。
2.克隆了山羊BLG基因3个不同长度的5’端调控序列片段，并分别插入到荧光报告载体pAdTrack-RFP中，构建了重组腺病毒载体：pAd-B51RFP、pAd-B52RFP和pAd-B53RFP，以这3个片段为调控序列来启动mRFP基因的表达。将包装得到的重组腺病毒分别感染山羊乳腺上皮细胞，用倒置荧光显微镜检测mRFP表达。结果表明3个片段均能够启动mRFP的表达，其中B51和B52启动mRFP的表达水平高于B53。
3.构建了4个靶向山羊BLG基因的打靶载体pBAT、pBATGFP、pBATM和pBAcT。其中pBATGFP含有neo和GFP两个阳性筛选标记基因，其他3个均只含有neo一个阳性筛选标记基因；pBATM的两个同源臂长度较pBAT短； pBAcT与pBATM载体的差异在于前者的目的基因为hALA cDNA。经酶切和测序鉴定，4个载体序列组装正确。以pBATM为代表，用其中的表达元件BLG基因5’调控序列、目的基因hALA和3’端调控序列置换pAdTrack-RFP中的mRFP和polyA，构建重组腺病毒载体。将包装得到的重组腺病毒感染山羊乳腺上皮细胞，用促乳素、EGF、胰岛素等进行诱导，取培养上清进行Western杂交检测，结果表明hALA能够在BLG基因调控序列指导下表达。
4.将构建的4个打靶载体及本实验室保存的旨在敲除山羊BLG基因的打靶载体pBLG2T线性化后分别转染山羊胎儿成纤维细胞，用G418和GCV进行药物筛选。结果发现从pBATGFP组筛选到的胎儿成纤维细胞中GFP表达量非常微弱，不能实现剔除野生型细胞污染的目的。在pBAT和pBLG2T两组中分别筛选鉴定得到2株（B412F1和B7732F6）和3株（T229F2，T1041F1，T7963F6）打靶细胞。
5.以5株打靶阳性细胞作为核供体进行体细胞核移植，将早期卵裂基因打靶克隆胚胎移植到同期发情的受体山羊输卵管，45d左右妊娠率达到了44.4%。妊娠足月顺产获得3只克隆山羊胎儿。经PCR及Southern杂交检测，其中有一只为BLG基因敲除山羊胎儿，另有一只为hALA定位整合的基因打靶阳性山羊。
Production of transgenic domestic animals which can be used to produce pharmaceuticalproteins or humanized milk is the popular research topics in recent years. Target genes can beknockout to disrupt its expression and the interested gene can be inserted into the specificlocus of the genome and expressed under the control of the internal regulatory elements withgene targeting techniques. As the main whey proteins in human milk, α-lactalbumin (ALA)was thought as the rich sources of essential amino acids, such as tryptophan, lysine andcysteine, especially for infants. It has been found that ALA may take part in the prevention ofgastrointestinal infections among neonates. In addition, as the main whey protein of theruminant milk, BLG was not contained in the milk of the human, and was considered as themain allergen of the cattle or goat milk. With the aim of producing transgenic goat which cansecrete humanized milk, we want to knockout the BLG gene in goat and/or to replace it withhALA using the gene targeting combined with somatic cell nuclear transfer techniques.
1. Firstly, we cloned the human ALA gene by PCR with serum genomic DNA as template.Meanwhile, in order to clone the cDNA of hALA, we integrated the hALA into the eukaryoticexpression vector pIRES2-EGFP. Then, the vector was transfected into the293T cells toconstruct the surrogate cells from which the total RNAs were extracted to clone the cDNA byRT-PCR. This protocol can be served as an alternative method to clone cDNA which onlyexpressed in the tissues not so conveniently to collect.
2. Three fragments of BLG in goat were cloned by PCR, and inserted into the fluorescentreporter vector pAdTrack-RFP. After recombination with pAdEasy-1in BJ5183, theadenoviral vector pAd-B51RFP, pAd-B52RFP and pAd-B53RFP were constructed in whichthe expression of mRFP was directed by the regulatory element, respectively. Then theadenovirus were packaged and used to infect the goat mammary epithelial cells. Wheninduced with corresponding hormones the expression of mRFP can be dtectected in the goatmammary epithelial cells, which showed that the BLG fragments were cloned successfully.
3. Four targeting vectors pBAT, pBATGFP, pBATM and pBAcT were constructedsuccessfully identified by enzymic digestion and sequencing. In order to assay the expressional elements in pBATM, the hALA combined with5’ and3’ flanking regions of BLGin pBATM was sub-cloned to replace the RFPPA in pAdTrack-RFP to construct theadenovirus. Induction the lactation of goat mammary epithelial cells infected with theadenovirus. The hALA was detected by western bloting in the culture medium, which furtherdemonstrated that the pBATM were constructed correctly.
4. Transfecting the goat fibroblast cells with the linearized four targeting vector andknockout vector pBLG2T, respectively. After selection with G418combined with ganciclovir(GCV),2(B412F1and B7732F6） and3(T229F2, T1041F1and T7963F6） strains of usabletargeted cells with normal karyotype were got in the group transfected with pBAT or pBLG2T,respectively. Unfortunately, GFP almostly cannot be detected in the clones transfected withpBATGFP, which suggested that it cannot be used to reject the contaminant wild cells mixedin the selected positive cell strains.
5. With the cells from the five selected targeted strains as donors, the recombinantembryos were transferred into the oviducts of the recipient goats after cultured24h in vitro.Totally about18goats were transferred and8pregnant goats were detected about45dayslater and3full term development fetuses were got finally. After detection with PCR andsouthern blot, one fetus was BLG knockout and one was hALA targeted integrated.
引文
陈红星,程萱,扬晓,邓继先,苏国富,黄培堂.2001.牛beta-乳球蛋白基因调控序列指导组织型纤溶酶原激活剂在小鼠乳腺中的表达.生物工程学报,17(2):135-139.
成勇,王玉阁.2002.由成年转基因山羊体细胞而来的克隆山羊.生物工程学报,18(1):79-83.
谷欣,黎燕.2005.位点特异性重组技术研究进展.生物技术通讯,16(4):417-419.
黄淑帧,黄英,陈美珏,陈巍,黄赞,李华,李景春,任兆瑞,曾溢滔.2000.转人血清白蛋白基因试管牛的研究.遗传学报,27(7):573-579.
黎丽荣,黄海军,高其双,董斌科,邓兵,刘艳,陶弼菲,向敏,吴建英,蒋思文.2009.猪PBD-1基因乳腺特异性表达载体的构建.生物技术通报,(5):127-129.
潘玲,徐冲.1999.人促红细胞生成素在转基因小鼠乳汁中表达.生物工程学报,15(1):28-34.
王宁,陈晓光,姚纪花,沈琦,薛京伦.2003.利用精原干细胞建立人凝血因子Ⅸ转基因小鼠.科学通报,48(17):1848-1850.
王勇胜.2009.优化核移植技术并生产转人溶菌酶和β-防御素-3克隆牛的研究.[博士学位论文].杨凌：西北农林科技大学.
吴庆侠,王爱华,司永嘉,周丽梅,盛宏霞,靳亚平.2010.山羊子宫内膜上皮细胞转染pCI-neo-hTERT质粒后的永生化.中国兽医学报,(2):228-232.
徐曼妮,厉曙光,赵建阳,成国祥.2004.乳腺生物反应器表达载体的检测方法.生物技术通报,(5):23-26.
杨焕明.2005.基因的分子生物学.北京:科学出版社.
杨晓,黄培堂,黄翠芬.2003.基因打靶技术.北京:科学出版社.
袁建刚,彭小忠,强伯勤.2009.基因组.北京:科学出版社.
张爱民,陈建泉,刘思国,沙红英,徐旭俊,吴友兵,陈娟,成国祥.2007.乳腺特异高表达人促红细胞生成素转基因奶山羊的制备.中国比较医学杂志,17(8):439-443.
张鹏宇,张艳玲,荆玉明,张信基,张哲欢,黎诚耀,陈白虹,谭万龙,李红卫.2011.南方医科大学学报,31(2):234-238.
赵新淮,于国萍,张永忠,李铁晶.2007.乳品化学.北京:科学出版社.
郑敬民,李坚,傅继梁.2000.重组酶介导的盒式交换及其应用.生命的化学,20(6):268-270.
Akshey, Y. S., Malakar, D., De, A. K., Jena, M. K., Sahu, S., Dutta, R.2011. Study of the efficiency ofchemically assisted enucleation method for handmade cloning in goat (Capra hircus). ReprodDomest Anim,46(4):699-704.
Alves, J., Vennekohl, P.2004. Protein engineering of restriction enzymes. In Restriction Endonucleases, pp.393-411.
Anand, T., Kumar, D., Singh, M. K., Shah, R. A., Chauhan, M. S., Manik, R. S., Singla, S. K., Palta, P.2011. Buffalo (Bubalus bubalis) Embryonic Stem Cell-Like Cells and Preimplantation EmbryosExhibit Comparable Expression of Pluripotency-Related Antigens. Reprod Domest Anim,46(1):50-58.
Araki, K., Okada, Y., Araki, M., Yamamura, K.2010. Comparative analysis of right element mutant loxsites on recombination efficiency in embryonic stem cells. BMC Biotechnol,10:29.
Arimondo, P. B., Thomas, C. J., Oussedik, K., Baldeyrou, B., Mahieu, C., Halby, L., Guianvarc'h, D.,Lansiaux, A., Hecht, S. M., Bailly, C., Giovannangeli, C.2006. Exploring the cellular activity ofcamptothecin-triple-helix-forming oligonucleotide conjugates. Mol Cell Biol,26(1):324-333.
Armstrong, L., Lako, M., Dean, W., Stojkovic, M.2006. Epigenetic modification is central to genomereprogramming in somatic cell nuclear transfer. Stem Cells,24(4):805-814.
Aston, K. I., Li, G. P., Hicks, B. A., Sessions, B. R., Davis, A. P., Rickords, L. F., Stevens, J. R., White, K. L.2010. Abnormal Levels of Transcript Abundance of Developmentally Important Genes in VariousStages of Preimplantation Bovine Somatic Cell Nuclear Transfer Embryos. CellularReprogramming,12(1):23-32.
Asuri, P., Bartel, M. A., Vazin, T., Jang, J. H., Wong, T. B., Schaffer, D. V.2012. Directed evolution ofadeno-associated virus for enhanced gene delivery and gene targeting in human pluripotent stemcells. Mol Ther,20(2):329-338.
Baguisi, A., Behboodi, E., Melican, D. T., Pollock, J. S., Destrempes, M. M., Cammuso, C., Williams, J. L.,Nims, S. D., Porter, C. A., Midura, P., Palacios, M. J., Ayres, S. L., Denniston, R. S., Hayes, M. L.,Ziomek, C. A., Meade, H. M., Godke, R. A., Gavin, W. G., Overstrom, E. W., Echelard, Y.1999.Production of goats by somatic cell nuclear transfer. Nat Biotechnol,17(5):456-461.
Banuelos, C. A., Banath, J. P., MacPhail, S. H., Zhao, J., Eaves, C. A., O'Connor, M. D., Lansdorp, P. M.,Olive, P. L.2008. Mouse but not human embryonic stem cells are deficient in rejoining of ionizingradiation-induced DNA double-strand breaks. DNA Repair (Amst),7(9):1471-1483.
Barbana, C., Sanchez, L., Perez, M. D.2011. Bioactivity of alpha-lactalbumin related to its interaction withfatty acids: a review. Crit Rev Food Sci Nutr,51(8):783-794.
Bath, A. J., Milsom, S. E., Gormley, N. A., Halford, S. E.2002. Many type IIs restriction endonucleasesinteract with two recognition sites before cleaving DNA. J Biol Chem,277(6):4024-4033.
Behboodi, E., Bondareva, A., Begin, I., Rao, K., Neveu, N., Pierson, T., Wylie, C., Piero, F. D., Huang, Y. J.,Zeng, W., Tanco, V., Baldassarre, H., Karatzas, C. N., Dobrinski, I.2011. Establishment of GoatEmbryonic Stem Cells From In Vivo Produced Blastocyst-Stage Embryos. Mol Reprod Dev,78(3):202-211.
Bibikova, M., Carroll, D., Segal, D. J., Trautman, J. K., Smith, J., Kim, Y. G., Chandrasegaran, S.2001.Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. MolCell Biol,21(1):289-297.
Bibikova, M., Golic, M., Golic, K. G., Carroll, D.2002. Targeted chromosomal cleavage and mutagenesisin Drosophila using zinc-finger nucleases. Genetics,161(3):1169-1175.
Bitinaite, J., Wah, D. A., Aggarwal, A. K., Schildkraut, I.1998. FokⅠdimerization is required for DNAcleavage. Proc Natl Acad Sci U S A,95(18):10570-10575.
Bleck, G. T., Bremel, R. D.1994. Variation in expression of a bovine alpha-lactalbumin transgene in milkof transgenic mice. J Dairy Sci,77(7):1897-1904.
Bleck, G. T., White, B. R., Miller, D. J., Wheeler, M. B.1998. Production of bovine alpha-lactalbumin inthe milk of transgenic pigs. J Anim Sci,76(12):3072-3078.
Boch, J., Scholze, H., Schornack, S., Landgraf, A., Hahn, S., Kay, S., Lahaye, T., Nickstadt, A., Bonas, U.2009. Breaking the code of DNA binding specificity of TAL-type Ⅲ effectors. Science,326(5959):1509-1512.
Bogdanove, A. J., Schornack, S., Lahaye, T.2010. TAL effectors: finding plant genes for disease anddefense. Curr Opin Plant Biol,13(4):394-401.
Brophy, B., Smolenski, G., Wheeler, T., Wells, D., L'Huillier, P., Laible, G.2003. Cloned transgenic cattleproduce milk with higher levels of beta-casein and kappa-casein. Nat Biotechnol,21(2):157-162.
Brown, J. P., Wei, W. Y., Sedivy, J. M.1997. Bypass of senescence after disruption of p21(CIP1/WAF1)gene in normal diploid human fibroblasts. Science,277(5327):831-834.
Bruck, W. M., Kelleher, S. L., Gibson, G. R., Graverholt, G., Lonnerdal, B. L.2006. The effects ofalpha-lactalbumin and glycomacropeptide on the association of CaCo-2cells by enteropathogenicEscherichia coli, Salmonella typhimurium and Shigella flexneri. FEMS Microbiol Lett,259(1):158-162.
Buehr, M., Meek, S., Blair, K., Yang, J., Ure, J., Silva, J., McLay, R., Hall, J., Ying, Q. L., Smith, A.2008.Capture of authentic embryonic stem cells from rat blastocysts. Cell,135(7):1287-1298.
Byrne, J. A., Pedersen, D. A., Clepper, L. L., Nelson, M., Sanger, W. G., Gokhale, S., Wolf, D. P., Mitalipov,S. M.2007. Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature,450(7169):497-502.
Cai, C. Q., Doyon, Y., Ainley, W. M., Miller, J. C., Dekelver, R. C., Moehle, E. A., Rock, J. M., Lee, Y. L.,Garrison, R., Schulenberg, L., Blue, R., Worden, A., Baker, L., Faraji, F., Zhang, L., Holmes, M. C.,Rebar, E. J., Collingwood, T. N., Rubin-Wilson, b., Gregory, P. D., Urnov, F. D., Petolino, J. F.,2009. Targeted transgene integration in plant cells using designed zinc finger nucleases. Plant MolBiol,69(6):699-709.
Campbell, K. H., McWhir, J., Ritchie, W. A., Wilmut, I.1996. Sheep cloned by nuclear transfer from acultured cell line. Nature,380(6569):64-66.
Cannata, F., Brunet, E., Perrouault, L., Roig, V., Ait-Si-Ali, S., Asseline, U., Concordet, J. P., Giovannangeli,C.2008. Triplex-forming oligonucleotide-orthophenanthroline conjugates for efficient targetedgenome modification. Proc Natl Acad Sci U S A,105(28):9576-9581.
Capecchi, M. R.2005. Gene targeting in mice: functional analysis of the mammalian genome for thetwenty-first century. Nat Rev Genet,6(6):507-512.
Carbery, I. D., Ji, D., Harrington, A., Brown, V., Weinstein, E. J., Liaw, L., Cui, X.2010. Targeted genomemodification in mice using zinc-finger nucleases. Genetics,186(2):451-459.
Carlson, D. F., Garbe, J. R., Tan, W., Martin, M. J., Dobrinsky, J. R., Hackett, P. B., Clark, K. J.,Fahrenkrug, S. C.2011. Strategies for selection marker-free swine transgenesis using the SleepingBeauty transposon system. Transgenic Res,20(5):1125-1137.
Catto, L. E., Ganguly, S., Milsom, S. E., Welsh, A. J., Halford, S. E.2006. Protein assembly and DNAlooping by the FokI restriction endonuclease. Nucleic Acids Res,34(6):1711-1720.
Cermak, T., Doyle, E. L., Christian, M., Wang, L., Zhang, Y., Schmidt, C., Baller, J. A., Somia, N. V.,Bogdanove, A. J., Voytas, D. F.2011. Efficient design and assembly of custom TALEN and otherTAL effector-based constructs for DNA targeting. Nucleic Acids Res,39(12):e82.
Cervera, R. P., Marti-Gutierrez, N., Escorihuela, E., Moreno, R., Stojkovic, M.2009. Trichostatin A affectshistone acetylation and gene expression in porcine somatic cell nucleus transfer embryos.Theriogenology,72(8):1097-1110.
Chang, K., Qian, J., Jiang, M., Liu, Y. H., Wu, M. C., Chen, C. D., Lai, C. K., Lo, H. L., Hsiao, C. T.,Brown, L., Bolen, J. Jr., Huang, H. I., Ho, P. Y., Shih, P. Y., Yao, C. H., Wu, F. Y., Lin, Y. J., Xu, J.,Wang, K.2002. Effective generation of transgenic pigs and mice by linker based sperm-mediatedgene transfer. BMC Biotechnol,2:5.
Chavatte-Palmer, P., Camous, S., Jammes, H., Le Cleac'h, N., Guillomot, M., Leed, R. S. F.2012. Review:Placental perturbations induce the developmental abnormalities often observed in bovine somaticcell nuclear transfer. Placenta,33:S99-S104.
Chesne, P., Adenot, P. G., Viglietta, C., Baratte, M., Boulanger, L., Renard, J. P.2002. Cloned rabbitsproduced by nuclear transfer from adult somatic cells. Nat Biotechnol,20(4):366-369.
Chi, H. Y., Shinohara, M., Yokomine, T., Sato, M., Takao, S., Yoshida, M., Miyoshi, K.2012. SuccessfulSuppression of Endogenous alpha-1,3-Galactosyltransferase Expression by RNA Interference inPig Embryos Generated In Vitro. J Reprod Dev,58(1):69-76.
Choulika, A., Perrin, A., Dujon, B., Nicolas, J. F.1995. Induction of homologous recombination inmammalian chromosomes by using the I-SceI system of Saccharomyces cerevisiae. Mol Cell Biol,15(4):1968-1973.
Cibelli, J. B., Stice, S. L., Golueke, P. J., Kane, J. J., Jerry, J., Blackwell, C., Ponce de Leon, F. A., Robl, J.M.1998. Transgenic bovine chimeric offspring produced from somatic cell-derived stem-like cells.Nat Biotechnol,16(7):642-646.
Clark, A. J., Ferrier, P., Aslam, S., Burl, S., Denning, C., Wylie, D., Ross, A., de Sousa, P., Wilmut, I., Cui,W.2003. Proliferative lifespan is conserved after nuclear transfer. Nat Cell Biol,5(6):535-538.
Clark, K. J., Carlson, D. F., Foster, L. K., Kong, B. W., Foster, D. N., Fahrenkrug, S. C.2007. Enzymaticengineering of the porcine genome with transposons and recombinases. BMC Biotechnol,7:42.
Constant, F., Guillomot, M., Heyman, Y., Vignon, X., Laigre, P., Servely, J. L., Renard, J. P.,Chavatte-Palmer, P.2006. Large offspring or large placenta syndrome? Morphometric analysis oflate gestation bovine placentomes from somatic nuclear transfer pregnancies complicated byhydrallantois. Biol Reprod,75(1):122-130.
Couldrey, C., Lee, R. S. F.2010. DNA methylation patterns in tissues from mid-gestation bovine foetusesproduced by somatic cell nuclear transfer show subtle abnormalities in nuclear reprogramming.BMC Dev Biol,10:27.
Counter, C. M., Meyerson, M., Eaton, E. N., Ellisen, L. W., Caddle, S. D., Haber, D. A., Weinberg, R. A.1998. Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), thecatalytic subunit of telomerase. Oncogene,16(9):1217-1222.
Cui, W., Wylie, D., Aslam, S., Dinnyes, A., King, T., Wilmut, I., Clark, A. J.2003.Telomerase-immortalized sheep fibroblasts can be reprogrammed by nuclear transfer to undergoearly development. Biol Reprod,69(1):15-21.
Cui, X., Ji, D., Fisher, D. A., Wu, Y., Briner, D. M., Weinstein, E. J.2011. Targeted integration in rat andmouse embryos with zinc-finger nucleases. Nat Biotechnol,29(1):64-7.
Cummins, J. M., Kohli, M., Rago, C., Kinzler, K. W., Vogelstein, B., Bunz, F.2004a. X-linked inhibitor ofapoptosis protein (XIAP) is a nonredundant modulator of tumor necrosis factor-relatedapoptosis-inducing ligand (TRAIL)-mediated apoptosis in human cancer cells. Cancer Res,64(9):3006-3008.
Cummins, J. M., Rago, C., Kohli, M., Kinzler, K. W., Lengauer, C., Vogelstein, B.2004b. Tumoursuppression: disruption of HAUSP gene stabilizes p53. Nature,428(6982):1p following486.
Curtin, S. J., Zhang, F., Sander, J. D., Haun, W. J., Starker, C., Baltes, N. J., Reyon, D., Dahlborg, E. J.,Goodwin, M. J., Coffman, A. P., Dobbs, D., Joung, J. K., Voytas, D. F., Stupar, R. M.2011.Targeted mutagenesis of duplicated genes in soybean with zinc-finger nucleases. Plant Physiol,156(2):466-473.
Dai, Y. F., Vaught, T. D., Boone, J., Chen, S. H., Phelps, C. J., Ball, S., Monahan, J. A., Jobst, P. M.,McCreath, K. J., Lamborn, A. E., Cowell-lucero, J. L., Wells, K. D., Colman, A., Polejaeva, I. A.,Ayares, D. L.2002. Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs.Nat Biotechnol,20(3):251-255.
Davis, L., Maizels, N.2011. DNA nicks promote efficient and safe targeted gene correction. PLoS One,6(9):e23981.
de Freitas, E. R. L., Sanches, B. V., Gambarini, M. L., Oliveira, B. D., Guillo, L. A.2011. EmbryonicStem-like Cells Derived from in vitro Produced Bovine Blastocysts. Brazi Arch Biol Techn,54(3):495-502.
de Souza, T. A., Soprano, A. S., de Lira, N. P., Quaresma, A. J., Pauletti, B. A., Paes Leme, A. F., Benedetti,C. E.2012. The TAL effector PthA4interacts with nuclear factors involved in RNA-dependentprocesses including a HMG protein that selectively binds poly(U) RNA. PLoS One,7(2):e32305.
Dean, D. A., Strong, D. D., Zimmer, W. E.2005. Nuclear entry of nonviral vectors. Gene Ther,12(11):881-890.
Deng, D., Yan, C., Pan, X., Mahfouz, M., Wang, J., Zhu, J. K., Shi, Y., Yan, N.2012. Structural basis forsequence-specific recognition of DNA by TAL effectors. Science,335(6069):720-723.
Denning, C., Burl, S., Ainslie, A., Bracken, J., Dinnyes, A., Fletcher, J., King, T., Ritchie, M., Ritchie, W.A., Rollo, M., de Sousa, P., Travers, A., Wilmut, I., Clark, A. J.2001a. Deletion of thealpha(1,3)galactosyl transferase (GGTA1) gene and the prion protein (PrP) gene in sheep. NatBiotechnol,19(6):559-562.
Denning, C., Dickinson, P., Burl, S., Wylie, D., Fletcher, J., Clark, A. J.2001b. Gene targeting in primaryfetal fibroblasts from sheep and pig. Cloning Stem Cells,3(4):221-231.
Dieckhoff, B., Karlas, A., Hofmann, A., Kues, W. A., Petersen, B., Pfeifer, A., Niemann, H., Kurth, R.,Denner, J.2007. Inhibition of porcine endogenous retroviruses (PERVs) in primary porcine cellsby RNA interference using lentiviral vectors. Arch Virol,152(3):629-634.
Dieckhoff, B., Petersen, B., Kues, W. A., Kurth, R., Niemann, H., Denner, J.2008. Knockdown of porcineendogenous retrovirus (PERV) expression by PERV-specific shRNA in transgenic pigs.Xenotransplantation,15(1):36-45.
Ding, X., Wang, Y., Zhang, D., Guo, Z., Zhang, Y.2008a. Increased pre-implantation development ofcloned bovine embryos treated with5-aza-2'-deoxycytidine and trichostatin A. Theriogenology,70(4):622-630.
Ding, X., Wang, Y., Zhang, D., Guo, Z., Zhang, Y.2008b. Increased pre-implantation development ofcloned bovine embryos treated with5-aza-2'-deoxycytidine and trichostatin A. Theriogenology,70(4):622-630.
Doerfler, W., Schubbert, R., Heller, H., Kammer, C., Hilger-Eversheim, K., Knoblauch, M., Remus, R.1997. Integration of foreign DNA and its consequences in mammalian systems. Trends Biotechnol,15(8):297-301.
Dominguez-Bendala, J., McWhir, J.2004. Enhanced gene targeting frequency in ES cells with lowgenomic methylation levels. Transgenic Res,13(1):69-74.
Dong, Z., Ge, J., Li, K., Xu, Z., Liang, D., Li, J., Jia, W., Li, Y., Dong, X., Cao, S., Wang, X., Pan, J., Zhao,Q.2011. Heritable Targeted Inactivation of Myostatin Gene in Yellow Catfish (Pelteobagrusfulvidraco) Using Engineered Zinc Finger Nucleases. PLoS One,6(12):e28897.
Donovan, D. M., Kerr, D. E., Wall, R. J.2005. Engineering disease resistant cattle. Transgenic Res,14(5):563-567.
Doyon, Y., McCammon, J. M., Miller, J. C., Faraji, F., Ngo, C., Katibah, G. E., Amora, R., Hocking, T. D.,Zhang, L., Rebar, E. J., Gregory, P. D. Urnov, F. D., Amacher, S. L.2008. Heritable targeted genedisruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol,26(6):702-708.
Dreier, B., Beerli, R. R., Segal, D. J., Flippin, J. D., Barbas, C. F.,3rd.2001. Development of zinc fingerdomains for recognition of the5'-ANN-3' family of DNA sequences and their use in theconstruction of artificial transcription factors. J Biol Chem,276(31):29466-29478.
Dreier, B., Fuller, R. P., Segal, D. J., Lund, C. V., Blancafort, P., Huber, A., Koksch, B., Barbas, C. F.,3rd.2005. Development of zinc finger domains for recognition of the5'-CNN-3' family DNAsequences and their use in the construction of artificial transcription factors. J Biol Chem,280(42):35588-35597.
Duca, M., Guianvarc'h, D., Oussedik, K., Halby, L., Garbesi, A., Dauzonne, D., Monneret, C., Osheroff, N.,Giovannangeli, C., Arimondo, P. B.2006. Molecular basis of the targeting of topoisomeraseII-mediated DNA cleavage by VP16derivatives conjugated to triplex-forming oligonucleotides.Nucleic Acids Res,34(6):1900-1911.
Echelard, Y., Williams, J. L., Destrempes, M. M., Koster, J. A., Overton, S. A., Pollock, D. P., Rapiejko, K.T., Behboodi, E., Masiello, N. C., Gavin, W. G., Pommer, J., Van Patten, S. M., Faber, D. C.,Cibelli, J. B., Meade, H. M.2009. Production of recombinant albumin by a herd of clonedtransgenic cattle. Transgenic Res,18(3):361-376.
Eisenschmidt, K., Lanio, T., Simoncsits, A., Jeltsch, A., Pingoud, V., Wende, W., Pingoud, A.2005.Developing a programmed restriction endonuclease for highly specific DNA cleavage. NucleicAcids Res,33(22):7039-7047.
Enright, B. P., Kubota, C., Yang, X., Tian, X. C.2003. Epigenetic characteristics and development ofembryos cloned from donor cells treated by trichostatin a or5-aza-2'-deoxycytidine. Biol Reprod,69(3):896-901.
Enright, B. P., Sung, L. Y., Chang, C. C., Yang, X., Tian, X. C.2005. Methylation and acetylationcharacteristics of cloned bovine embryos from donor cells treated with5-aza-2'-deoxycytidine.Biol Reprod,72(4):944-948.
Esteban, M. A., Xu, J., Yang, J., Peng, M., Qin, D., Li, W., Jiang, Z., Chen, J., Deng, K., Zhong, M., Cai, J.,Lai, L., Pei, D.2009. Generation of induced pluripotent stem cell lines from Tibetan miniature pig.J Biol Chem,284(26):17634-17640.
Ezashi, T., Telugu, B. P., Alexenko, A. P., Sachdev, S., Sinha, S., Roberts, R. M.2009. Derivation ofinduced pluripotent stem cells from pig somatic cells. Proc Natl Acad Sci U S A,106(27):10993-10998.
Fajardo-Sanchez, E., Stricher, F., Paques, F., Isalan, M., Serrano, L.2008. Computer design of obligateheterodimer meganucleases allows efficient cutting of custom DNA sequences. Nucleic Acids Res,36(7):2163-2173.
Fan, H. F.2012. Real-time single-molecule tethered particle motion experiments reveal the kinetics andmechanisms of Cre-mediated site-specific recombination. Nucleic Acids Res, in press, doi:10.1093/nar/gks274.
Fisher, E. W., Yang, M. T., Jeng, S. T., Gardner, J. F., Gumport, R. I.1995. Selection of mutations alteringspecificity in restriction-modification enzymes using the bacteriophage P22challenge-phagesystem. Gene,157(1-2):119-121.
Flisikowska, T., Thorey, I. S., Offner, S., Ros, F., Lifke, V., Zeitler, B., Rottmann, O., Vincent, A., Zhang, L.,Jenkins, S., Niersbach, H., Kind, A. J., Gregory, P. D., Schnieke, A. E., Platzer, J.2011. Efficientimmunoglobulin gene disruption and targeted replacement in rabbit using zinc finger nucleases.PLoS One,6(6):e21045.
Fujiwara, Y., Takahashi, R. I., Miwa, M., Kameda, M., Kodaira, K., Hirabayashi, M., Suzuki, T., Ueda, M.1999. Analysis of control elements for position-independent expression of humanalpha-lactalbumin YAC. Mol Reprod Dev,54(1):17-23.
Fulka, J., Miyashita, N., Nagai, T., Ogura, A.2004. Do cloned mammals skip a reprogramming step? NatBiotechnol,22(1):25-26.
Gabriel, R., Lombardo, A., Arens, A., Miller, J. C., Genovese, P., Kaeppel, C., Nowrouzi, A., Bartholomae,C. C., Wang, J., Friedman, G., Holmes, M. C., Gregory, P. D., Glimm, H., Schmidt, M., Naldini, L.,von Kalle, C.2011. An unbiased genome-wide analysis of zinc-finger nuclease specificity. NatBiotechnol,29(9):816-823.
Galetto, R., Duchateau, P., Paques, F.2009. Targeted approaches for gene therapy and the emergence ofengineered meganucleases. Expert Opin Biol Ther,9(10):1289-1303.
Galli, C., Lagutina, I., Crotti, G., Colleoni, S., Turini, P., Ponderato, N., Duchi, R., Lazzari, G.2003.Pregnancy: a cloned horse born to its dam twin. Nature,424(6949):635.
Garrels, W., Holler, S., Taylor, U., Herrmann, D., Struckmann, C., Klein, S., Barg-Kues, B., Nowak-Imialek,M., Ehling, C., Rath, D., Ivics, Z., Niemann, H., Kues, W. A.2011. Genotype-independenttransmission of transgenic fluorophore protein by boar spermatozoa. PLoS One,6(11):e27563.
Gemmen, G. J., Millin, R., Smith, D. E.2006a. DNA looping by two-site restriction endonucleases:heterogeneous probability distributions for loop size and unbinding force. Nucleic Acids Res,34(10):2864-2877.
Gemmen, G. J., Millin, R., Smith, D. E.2006b. Tension-dependent DNA cleavage by restrictionendonucleases: two-site enzymes are "switched off" at low force. Proc Natl Acad Sci U S A,103(31):11555-11560.
George, A., Sharma, R., Singh, K. P., Panda, S. K., Singla, S. K., Palta, P., Manik, R., Chauhan, M. S.2011.Production of Cloned and Transgenic Embryos Using Buffalo (Bubalus bubalis) Embryonic StemCell-Like Cells Isolated from In Vitro Fertilized and Cloned Blastocysts. Cell Reprogram,13(3):263-272.
Geurts, A. M., Cost, G. J., Freyvert, Y., Zeitler, B., Miller, J. C., Choi, V. M., Jenkins, S. S., Wood, A., Cui,X., Meng, X., Vincent, A., Lam, S., Michalkiewicz, M., Schilling, R., Foeckler, J., Kalloway, S.,Weiler, H., Menoret, S., Anegon, I., Davis, G. D., Zhang, L., Rebar, E. J., Gregory, P. D., Urnov, F.D., Jacob, H. J., Buelow, R.2009. Knockout rats via embryo microinjection of zinc-fingernucleases. Science,325(5939):433.
Glaser, S., Anastassiadis, K., Stewart, A. F.2005. Current issues in mouse genome engineering. Nat Genet,37(11):1187-1193.
Golding, M. C., Long, C. R., Carmell, M. A., Hannon, G. J., Westhusin, M. E.2006. Suppression of prionprotein in livestock by RNA interference. Proc Natl Acad Sci U S A,103(14):5285-5290.
Golovan, S. P., Meidinger, R. G., Ajakaiye, A., Cottrill, M., Wiederkehr, M. Z., Barney, D. J., Plante, C.,Pollard, J. W., Fan, M. Z., Hayes, M. A., Laursen, J., Hjorth, J. P., Hacker, R. R., Phillips, J. P.,Forsberg, C. W.2001. Pigs expressing salivary phytase produce low-phosphorus manure. NatBiotechnol,19(8):741-745.
Gossen, M., Bujard, H.2002. Studying gene function in eukaryotes by conditional gene inactivation. AnnuRev Genet,36153-36173.
Graham, C., Cole, S., Laible, G.2009. Site-specific modification of the bovine genome using Crerecombinase-mediated gene targeting. Biotechnol J,4(1):108-118.
Grindley, N. D., Whiteson, K. L., Rice, P. A.2006. Mechanisms of site-specific recombination. Annu RevBiochem,75567-75605.
Grizot, S., Smith, J., Daboussi, F., Prieto, J., Redondo, P., Merino, N., Villate, M., Thomas, S., Lemaire, L.,Montoya, G., Blanco, F. J., Paques, F., Duchateau, P.2009. Efficient targeting of a SCID gene byan engineered single-chain homing endonuclease. Nucleic Acids Res,37(16):5405-5419.
Gu, K., Yang, B., Tian, D., Wu, L., Wang, D., Sreekala, C., Yang, F., Chu, Z., Wang, G. L., White, F. F., Yin,Z.2005. R gene expression induced by a type-III effector triggers disease resistance in rice. Nature,435(7045):1122-1125.
Gustafsson, L., Leijonhufvud, I., Aronsson, A., Mossberg, A. K., Svanborg, C.2004. Treatment of skinpapillomas with topical alpha-lactalbumin-oleic acid. N Engl J Med,350(26):2663-2672.
Gyurcsik, B., Czene, A.2011. Towards artificial metallonucleases for gene therapy: recent advances andnew perspectives. Future Med Chem,3(15):1935-1966.
Haber, J. E.2000. Partners and pathways: repairing a double-strand break. Trends Genet,16(6):259-264.
Hamanaka, S., Yamaguchi, T., Kobayashi, T., Kato-Itoh, M., Yamazaki, S., Sato, H., Umino, A., Wakiyama,Y., Arai, M., Sanbo, M., Hirabayashi, M., Nakauchi, H.2011. Generation of germline-competentrat induced pluripotent stem cells. PLoS One,6(7):e22008.
Hamm, A., Krott, N., Breibach, I., Blindt, R., Bosserhoff, A. K.2002. Efficient transfection method forprimary cells. Tissue Eng,8(2):235-245.
Hammer, R. E., Pursel, V. G., Rexroad, C. E., Jr., Wall, R. J., Bolt, D. J., Ebert, K. M., Palmiter, R. D.,Brinster, R. L.1985. Production of transgenic rabbits, sheep and pigs by microinjection. Nature,315(6021):680-683.
Hamra, F. K., Gatlin, J., Chapman, K. M., Grellhesl, D. M., Garcia, J. V., Hammer, R. E., Garbers, D. L.2002. Production of transgenic rats by lentiviral transduction of male germ-line stem cells. ProcNatl Acad Sci U S A,99(23):14931-14936.
Han, Z., Wu, S., Li, Q., Li, J., Gao, D., Li, K., Liu, Z. W., Zhao, H.2009. Efficient Human GrowthHormone Gene Expression in the Milk of Non-transgenic Goats. Folia Biol (Praha),55(1):17-22.
Hanson, K. D., Sedivy, J. M.1995. Analysis of biological selections for high-efficiency gene targeting. MolCell Biol,15(1):45-51.
Hasty, P., Rivera-Perez, J., Chang, C., Bradley, A.1991. Target frequency and integration pattern forinsertion and replacement vectors in embryonic stem cells. Mol Cell Biol,11(9):4509-4517.
Hauschild, J., Petersen, B., Santiago, Y., Queisser, A. L., Carnwath, J. W., Lucas-Hahn, A., Zhang, L.,Meng, X., Gregory, P. D., Schwinzer, R., Cost, G. J., Niemann, H.2011. Efficient generation of abiallelic knockout in pigs using zinc-finger nucleases. Proc Natl Acad Sci U S A,108(29):12013-1207.
He, Y. L., Wu, Y. H., He, X. N., Liu, F. J., He, X. Y., Zhang, Y.2009. An immortalized goat mammaryepithelial cell line induced with human telomerase reverse transcriptase (hTERT) gene transfer.Theriogenology,71(9):1417-1424.
Hickey, R. D., Lillegard, J. B., Fisher, J. E., McKenzie, T. J., Hofherr, S. E., Finegold, M. J., Nyberg, S. L.,Grompe, M.2011. Efficient production of Fah-null heterozygote pigs by chimericadeno-associated virus-mediated gene knockout and somatic cell nuclear transfer. Hepatology,54(4):1351-1359.
Hirata, R., Chamberlain, J., Dong, R., Russell, D. W.2002. Targeted transgene insertion into humanchromosomes by adeno-associated virus vectors. Nat Biotechnol,20(7):735-738.
Hirata, R. K., Xu, C., Dong, R., Miller, D. G., Ferguson, S., Russell, D. W.2004. Efficient PRNP genetargeting in bovine fibroblasts by adeno-associated virus vectors. Cloning Stem Cells,6(1):31-36.
Hockemeyer, D., Jaenisch, R.2010. Gene targeting in human pluripotent cells. Cold Spring Harb SympQuant Biol,75201-75209.
Hockemeyer, D., Soldner, F., Beard, C., Gao, Q., Mitalipova, M., DeKelver, R. C., Katibah, G. E., Amora,R., Boydston, E. A., Zeitler, B., Meng, X., Miller, J. C., Zhang, L., Rebar, E. J., Gregory, P. D.,Urnov, F. D., Jaenisch, R.2009. Efficient targeting of expressed and silent genes in human ESCsand iPSCs using zinc-finger nucleases. Nat Biotechnol,27(9):851-857.
Hofmann, A., Kessler, B., Ewerling, S., Weppert, M., Vogg, B., Ludwig, H., Stojkovic, M., Boelhauve, M.,Brem, G., Wolf, E., Pfeifer, A.2003. Efficient transgenesis in farm animals by lentiviral vectors.EMBO Rep,4(11):1054-1060.
Hofmann, A., Zakhartchenko, V., Weppert, M., Sebald, H., Wenigerkind, H., Brem, G., Wolf, E., Pfeifer, A.2004. Generation of transgenic cattle by lentiviral gene transfer into oocytes. Biol Reprod,71(2):405-409.
Holmes, A. M., Haber, J. E.1999. Double-strand break repair in yeast requires both leading and laggingstrand DNA polymerases. Cell,96(3):415-424.
Honaramooz, A., Megee, S., Zeng, W., Destrempes, M. M., Overton, S. A., Luo, J., Galantino-Homer, H.,Modelski, M., Chen, F., Blash, S., Melican, D. T., Gavin, W. G., Ayres, S., Yang, F., Wang, P. J.,Echelard, Y., Dobrinski, I.2008. Adeno-associated virus (AAV)-mediated transduction of malegerm line stem cells results in transgene transmission after germ cell transplantation. FASEB J,22(2):374-382.
Honda, A., Hirose, M., Hatori, M., Matoba, S., Miyoshi, H., Inoue, K., Ogura, A.2010. Generation ofinduced pluripotent stem cells in rabbits: potential experimental models for human regenerativemedicine. J Biol Chem,285(41):31362-31369.
Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A. E., Melton, D. A.2008a.Induction of pluripotent stem cells by defined factors is greatly improved by small-moleculecompounds. Nat Biotechnol,26(7):795-797.
Huangfu, D., Osafune, K., Maehr, R., Guo, W., Eijkelenboom, A., Chen, S., Muhlestein, W., Melton, D. A.2008b. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4andSox2. Nat Biotechnol,26(11):1269-1275.
Iager, A. E., Ragina, N. P., Ross, P. J., Beyhan, Z., Cunniff, K., Rodriguez, R. M., Cibelli, J. B.2008.Trichostatin a improves histone acetylation in bovine somatic cell nuclear transfer early embryos.Cloning Stem Cells,10(3):371-379.
Iiizumi, S., Kurosawa, A., So, S., Ishii, Y., Chikaraishi, Y., Ishii, A., Koyama, H., Adachi, N.2008. Impactof non-homologous end-joining deficiency on random and targeted DNA integration: implicationsfor gene targeting. Nucleic Acids Res,36(19):6333-6342.
Jafari, S., Hosseini, M. S., Hajian, M., Forouzanfar, M., Jafarpour, F., Abedi, P., Ostadhosseini, S., Abbasi,H., Gourabi, H., Shahverdi, A. H., Dizaj, A. V. T., Anjomshoaa, M., Haron, W., Noorshariza, N.,Yakub, H., Nasr-Esfahani, M. H.2011. Improved In Vitro Development of Cloned BovineEmbryos Using S-Adenosylhomocysteine, a Non-Toxic Epigenetic Modifying Reagent. MolReprod Dev,78(8):576-584.
Jafarpour, F., Hosseini, S. M., Hajian, M., Forouzanfar, M., Ostadhosseini, S., Abedi, P., Gholami, S.,Ghaedi, K., Gourabi, H., Shahverdi, A. H., Vosough, A. D. T., Nasr-Esfahani, M. H.2011. SomaticCell-Induced Hyperacetylation, But Not Hypomethylation, Positively and Reversibly Affects theEfficiency of In Vitro Cloned Blastocyst Production in Cattle. Cell Reprogram,13(6):483-493.
Jakobsen, J. E., Li, J., Kragh, P. M., Moldt, B., Lin, L., Liu, Y., Schmidt, M., Winther, K. D., Schyth, B. D.,Holm, I. E,, Vajta, G., Bolund, L., Callesen, H., Jorgensen, A. L., Nielsen, A. L., Mikkelsen, J. G.2011a. Pig transgenesis by Sleeping Beauty DNA transposition. Transgenic Res,20(3):533-545.
Jakobsen, J. E., Li, J., Moldt, B., Kragh, P. M., Callesen, H., Hertz, J. M., Bolund, L., Jorgensen, A. L.,Mikkelsen, J. G., Nielsen, A. L.2011b. Establishment of a pig fibroblast-derived cell line forlocus-directed transgene expression in cell cultures and blastocysts. Mol Biol Rep,38(1):151-61.
Johnson, J., Canning, J., Kaneko, T., Pru, J. K., Tilly, J. L.2004. Germline stem cells and follicular renewalin the postnatal mammalian ovary. Nature,428(6979):145-150.
Kalvala, A., Rainaldi, G., Di Primio, C., Liverani, V., Falaschi, A., Galli, A.2010. Enhancement of genetargeting in human cells by intranuclear permeation of the Saccharomyces cerevisiae Rad52protein. Nucleic Acids Res,38(14):e149.
Kanatsu-Shinohara, M., Kato, M., Takehashi, M., Morimoto, H., Takashima, S., Chuma, S., Nakatsuji, N.,Hirabayashi, M., Shinohara, T.2008. Production of transgenic rats via lentiviral transduction andxenogeneic transplantation of spermatogonial stem cells. Biol Reprod,79(6):1121-1128.
Kanatsu-Shinohara, M., Ogonuki, N., Inoue, K., Miki, H., Ogura, A., Toyokuni, S., Shinohara, T.2003.Long-term proliferation in culture and germline transmission of mouse male germline stem cells.Biol Reprod,69(2):612-616.
Kang, L., Wang, J., Zhang, Y., Kou, Z., Gao, S.2009. iPS cells can support full-term development oftetraploid blastocyst-complemented embryos. Cell Stem Cell,5(2):135-138.
Kato, Y., Tani, T., Sotomaru, Y., Kurokawa, K., Kato, J., Doguchi, H., Yasue, H., Tsunoda, Y.1998. Eightcalves cloned from somatic cells of a single adult. Science,282(5396):2095-2098.
Kay, S., Bonas, U.2009a. How Xanthomonas type III effectors manipulate the host plant. Curr OpinMicrobiol,12(1):37-43.
Kay, S., Hahn, S., Marois, E., Hause, G., Bonas, U.2007. A bacterial effector acts as a plant transcriptionfactor and induces a cell size regulator. Science,318(5850):648-651.
Kay, S., Hahn, S., Marois, E., Wieduwild, R., Bonas, U.2009b. Detailed analysis of the DNA recognitionmotifs of the Xanthomonas type III effectors AvrBs3and AvrBs3Deltarep16. Plant J,59(6):859-871.
Kim, D., Kim, C. H., Moon, J. I., Chung, Y. G., Chang, M. Y., Han, B. S., Ko, S., Yang, E., Cha, K. Y.,Lanza, R., Kim, K. S.2009. Generation of human induced pluripotent stem cells by direct deliveryof reprogramming proteins. Cell Stem Cell,4(6):472-476.
Kim, H., Um, E., Cho, S. R., Jung, C., Kim, J. S.2011. Surrogate reporters for enrichment of cells withnuclease-induced mutations. Nat Methods,8(11):941-943.
Kim, M. K., Jang, G., Oh, H. J., Yuda, F., Kim, H. J., Hwang, W. S., Hossein, M. S., Kim, J. J., Shin, N. S.,Kang, S. K., Lee, B. C.2007. Endangered wolves cloned from adult somatic cells. Cloning StemCells,9(1):130-137.
Kim, S. J., Sohn, B. H., Jeong, S., Pak, K. W., Park, J. S., Park, I. Y., Lee, T. H., Choi, Y. H., Lee, C. S.,Han, Y. M., Yu, D. Y., Lee, K. K.1999. High-level expression of human lactoferrin in milk oftransgenic mice using genomic lactoferrin sequence. J Biochem,126(2):320-325.
Kim, Y. G., Cha, J., Chandrasegaran, S.1996. Hybrid restriction enzymes: zinc finger fusions to Fok Icleavage domain. Proc Natl Acad Sci U S A,93(3):1156-1160.
Kim, Y. G., Chandrasegaran, S.1994. Chimeric restriction endonuclease. Proc Natl Acad Sci U S A,91(3):883-887.
Kim, Y. G., Smith, J., Durgesha, M., Chandrasegaran, S.1998. Chimeric restriction enzyme: Gal4fusion toFokI cleavage domain. Biol Chem,379(4-5):489-495.
Kishigami, S., Bui, H. T., Wakayama, S., Tokunaga, K., Thuan, N. V., Hikichi, T., Mizutani, E., Ohta, H.,Suetsugu, R., Sata, T., Wakayama, T.2007. Successful mouse cloning of an outbred strain bytrichostatin A treatment after somatic nuclear transfer. J Reprod Develop,53(1):165-170.
Kishigami, S., Mizutani, E., Ohta, H., Hikichi, T., Thuan, N. V., Wakayama, S., Bui, H. T., Wakayama, T.2006. Significant improvement of mouse cloning technique by treatment with trichostatin A aftersomatic nuclear transfer. Biochem Biophys Res Commun,340(1):183-189.
Klymiuk, N., Mundhenk, L., Kraehe, K., Wuensch, A., Plog, S., Emrich, D., Langenmayer, M. C., Stehr, M.,Holzinger, A., Kroner, C., Richter, A., Kessler, B., Kurome, M., Eddicks, M., Nagashima, H.,Heinritzi, K., Gruber, A. D., Wolf, E.2012. Sequential targeting of CFTR by BAC vectorsgenerates a novel pig model of cystic fibrosis. J Mol Med,90(5):597-608.
Kohli, M., Rago, C., Lengauer, C., Kinzler, K. W., Vogelstein, B.2004. Facile methods for generatinghuman somatic cell gene knockouts using recombinant adeno-associated viruses. Nucleic AcidsRes,32(1):e3.
Kolber-Simonds, D., Lai, L., Watt, S. R., Denaro, M., Arn, S., Augenstein, M. L., Betthauser, J., Carter, D.B., Greenstein, J. L., Hao, Y., Im, G. S., Liu, Z., Mell, G. D., Murphy, C. N., Park, K. W., Rieke, A.,Ryan, D. J., Sachs, D. H., Forsberg, E. J., Prather, R. S., Hawley, R. J.2004. Production ofalpha-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing lossof heterozygosity mutations. Proc Natl Acad Sci U S A,101(19):7335-7340.
Koller, B. H., Hagemann, L. J., Doetschman, T., Hagaman, J. R., Huang, S., Williams, P. J., First, N. L.,Maeda, N., Smithies, O.1989. Germ-line transmission of a planned alteration made in ahypoxanthine phosphoribosyltransferase gene by homologous recombination in embryonic stemcells. Proc Natl Acad Sci U S A,86(22):8927-8931.
Koller, B. H., Kim, H. S., Latour, A. M., Brigman, K., Boucher, R. C., Jr., Scambler, P., Wainwright, B.,Smithies, O.1991. Toward an animal model of cystic fibrosis: targeted interruption of exon10ofthe cystic fibrosis transmembrane regulator gene in embryonic stem cells. Proc Natl Acad Sci U SA,88(23):10730-10734.
Kragh, P. M., Nielsen, A. L., Li, J., Du, Y. T., Lin, L., Schmidt, M., Bogh, I. B., Holm, I. E., Jakobsen, J. E.,Johansen, M. G., Purup, S., Bolund, L, Vajta, G., Jorgensen, A. L.2009. Hemizygous minipigsproduced by random gene insertion and handmade cloning express the Alzheimer's disease-causingdominant mutation APPsw. Transgenic Res,18(4):545-558.
Kreb, J. E., Goldstein, E. S., Kilpatrick, S. T.2010. Lewin's Genes X.北京:高等教育出版社.
Kuroiwa, Y., Kasinathan, P., Choi, Y. J., Naeem, R., Tomizuka, K., Sullivan, E. J., Knott, J. G., Duteau, A.,Goldsby, R. A., Osborne, B. A., Ishida, I., Robl, J. M.2002. Cloned transchromosomic calvesproducing human immunoglobulin. Nat Biotechnol,20(9):889-894.
Kuroiwa, Y., Kasinathan, P., Matsushita, H., Sathiyaselan, J., Sullivan, E. J., Kakitani, M., Tomizuka, K.,Ishida, I., Robl, J. M.2004. Sequential targeting of the genes encoding immunoglobulin-mu andprion protein in cattle. Nat Genet,36(7):775-780.
Kuroiwa, Y., Kasinathan, P., Sathiyaseelan, T., Jiao, J. A., Matsushita, H., Sathiyaseelan, J., Wu, H.,Mellquist, J., Hammitt, M., Koster, J., Kamoda, A., Tachibana, K., Ishida, I., Robl, J. M.2009.Antigen-specific human polyclonal antibodies from hyperimmunized cattle. Nat Biotechnol,27(2):173-181.
Kurome, M., Hisatomi, H., Matsumoto, S., Tomii, R., Ueno, S., Hiruma, K., Saito, H., Nakamura, K.,Okumura, K., Matsumoto, M., Kaji, Y., Endo, F., Nagashima, H.2008. Production efficiency andtelomere length of the cloned pigs following serial somatic cell nuclear transfer. J Reprod Develop,54(4):254-258.
Lai, L. X., Kang, J. X., Li, R. F., Wang, J. D., Witt, W. T., Yong, H. Y., Hao, Y. H., Wax, D. M., Murphy, C.N., Rieke, A., Samuei, M., Linville, M. L., Korte, S. W., Evans, R W., Starzl, T. E., Prather, R. S.,Dai, Y. F.2006. Generation of cloned transgenic pigs rich in omega-3fatty acids. Nat Biotechnol,24(4):435-436.
Lai, L. X., Kolber-Simonds, D., Park, K. W., Cheong, H. T., Greenstein, J. L., Im, G. S., Samuel, M., Bonk,A., Rieke, A., Day, B. N., Murphy, C. N., Carter, D. B., Hawley, R. J., Prather, R. S.2002.Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer coning. Science,295(5557):1089-1092.
Laible, G., Alonso-Gonzalez, L.2009. Gene targeting from laboratory to livestock: current status andemerging concepts. Biotechnol J,4(9):1278-1292.
Lavitrano, M., Bacci, M. L., Forni, M., Lazzereschi, D., Di Stefano, C., Fioretti, D., Giancotti, P., Marfe, G.,Pucci, L., Renzi, L., Wang, H., Stoppacciaro, A., Stassi, g., Sargiacomo, M., Sinibaldi, P, Turchi, V.,Giovannoni, R., Della Casa, G., Seren, E., Rossi, G.2002. Efficient production by sperm-mediatedgene transfer of human decay accelerating factor (hDAF) transgenic pigs for xenotransplantation.Proc Natl Acad Sci U S A,99(22):14230-14235.
Lavitrano, M., Camaioni, A., Fazio, V. M., Dolci, S., Farace, M. G., Spadafora, C.1989. Sperm cells asvectors for introducing foreign DNA into eggs: genetic transformation of mice. Cell,57(5):717-723.
Le Provost, F., Lillico, S., Passet, B., Young, R., Whitelaw, B., Vilotte, J. L.2010. Zinc finger nucleasetechnology heralds a new era in mammalian transgenesis. Trends Biotechnol,28(3):134-141.
Lee, B. C., Kim, M. K., Jang, G., Oh, H. J., Yuda, F., Kim, H. J., Hossein, M. S., Kim, J. J., Kang, S. K.,Schatten, G., Hwang, W. S.2005. Dogs cloned from adult somatic cells. Nature,436(7051):641.
Leighton, P. A., van de Lavoir, M. C., Diamond, J. H., Xia, C., Etches, R. J.2008. Genetic modification ofprimordial germ cells by gene trapping, gene targeting, and phiC31integrase. Mol Reprod Dev,75(7):1163-1175.
Li, J., Baker, M. D.2000. Formation and repair of heteroduplex DNA on both sides of the double-strandbreak during mammalian gene targeting. J Mol Biol,295(3):505-516.
Li, J., Svarcova, O., Villemoes, K., Kragh, P. M., Schmidt, M., Bogh, I. B., Zhang, Y., Du, Y., Lin, L.,Purup, S., Xue, q., Bolund, L., Yang, H., Maddox-Hyttel, P., Vajta, G.2008a. High in vitrodevelopment after somatic cell nuclear transfer and trichostatin A treatment of reconstructedporcine embryos. Theriogenology,70(5):800-808.
Li, L., Chandrasegaran, S.1993a. Alteration of the cleavage distance of Fok I restriction endonuclease byinsertion mutagenesis. Proc Natl Acad Sci U S A,90(7):2764-2768.
Li, L., Wu, L. P., Chandrasegaran, S.1992. Functional domains in Fok I restriction endonuclease. Proc NatlAcad Sci U S A,89(10):4275-4279.
Li, L., Wu, L. P., Clarke, R., Chandrasegaran, S.1993b. C-terminal deletion mutants of the FokI restrictionendonuclease. Gene,133(1):79-84.
Li, P., Tong, C., Mehrian-Shai, R., Jia, L., Wu, N., Yan, Y., Maxson, R. E., Schulze, E. N., Song, H., Hsieh,C. L., Pera, M. F., Ying, Q. L.2008b. Germline competent embryonic stem cells derived from ratblastocysts. Cell,135(7):1299-1310.
Li, X., Heyer, W. D.2008c. Homologous recombination in DNA repair and DNA damage tolerance. CellRes,18(1):99-113.
Li, Z., Sun, X., Chen, J., Liu, X., Wisely, S. M., Zhou, Q., Renard, J. P., Leno, G. H., Engelhardt, J. F.2006.Cloned ferrets produced by somatic cell nuclear transfer. Dev Biol,293(2):439-448.
Liao, J., Cui, C., Chen, S., Ren, J., Chen, J., Gao, Y., Li, H., Jia, N., Cheng, L., Xiao, H., Xiao, L.2009.Generation of induced pluripotent stem cell lines from adult rat cells. Cell Stem Cell,4(1):11-5.
Lieber, M. R.2010. The mechanism of double-strand DNA break repair by the nonhomologous DNAend-joining pathway. Annu Rev Biochem,79181-79211.
Lieu, P. T., Machleidt, T., Thyagarajan, B., Fontes, A., Frey, E., Fuerstenau-Sharp, M., Thompson, D. V.,Swamilingiah, G. M., Derebail, S. S., Piper, D., Chesnut, J. D.2009. Generation of site-specificretargeting platform cell lines for drug discovery using phiC31and R4integrases. J Biomol Screen,14(10):1207-1215.
Lin, F. L., Sperle, K., Sternberg, N.1984. Model for homologous recombination during transfer of DNAinto mouse L cells: role for DNA ends in the recombination process. Mol Cell Biol,4(6):1020-34.
Lin, F. L., Sperle, K., Sternberg, N.1985. Recombination in mouse L cells between DNA introduced intocells and homologous chromosomal sequences. Proc Natl Acad Sci U S A,82(5):1391-1395.
Lin, Y., Lukacsovich, T., Waldman, A. S.1999. Multiple pathways for repair of DNA double-strand breaksin mammalian chromosomes. Mol Cell Biol,19(12):8353-8360.
Lippow, S. M., Aha, P. M., Parker, M. H., Blake, W. J., Baynes, B. M., Lipovsek, D.2009. Creation of atype IIS restriction endonuclease with a long recognition sequence. Nucleic Acids Res,37(9):3061-3073.
Liu, H., Zhu, F., Yong, J., Zhang, P., Hou, P., Li, H., Jiang, W., Cai, J., Liu, M., Cui, K., Qu, X., Xiang, T.,Lu, D., Chi, X., Gao, G., Ji, W., Ding, M., Deng, H.2008. Generation of induced pluripotent stemcells from adult rhesus monkey fibroblasts. Cell Stem Cell,3(6):587-590.
Liu, J., Jeppesen, I., Nielsen, K., Jensen, T. G.2006. Phi c31integrase induces chromosomal aberrations inprimary human fibroblasts. Gene Ther,13(15):1188-1190.
Liu, Q., Xia, Z., Zhong, X., Case, C. C.2002. Validated zinc finger protein designs for all16GNN DNAtriplet targets. J Biol Chem,277(6):3850-3856.
Liu, S., Li, X. Q., Lu, D., Shang, S. Z., Wang, M. L., Zheng, M., Zhang, R., Tang, B., Li, Q. Y., Dai, Y. P.,Li, N.2012. High-level expression of bioactive recombinant human lysozyme in the milk oftransgenic mice using a modified human lactoferrin BAC. Transgenic Res,21(2):407-414.
Liu, W. Y., Wang, Y., Qin, Y., Wang, Y. P., Zhu, Z. Y.2007. Site-directed gene integration in transgeniczebrafish mediated by cre recombinase using a combination of mutant lox sites. Mar Biotechnol(NY),9(4):420-428.
Loi, P., Ptak, G., Barboni, B., Fulka, J., Jr., Cappai, P., Clinton, M.2001. Genetic rescue of an endangeredmammal by cross-species nuclear transfer using post-mortem somatic cells. Nat Biotechnol,19(10):962-964.
Lombardo, A., Cesana, D., Genovese, P., Di Stefano, B., Provasi, E., Colombo, D. F., Neri, M., Magnani, Z.,Cantore, A., Lo Riso, P., Damo, M., Pello, O. M., Holmes, M. C., Gregory, P. D., Gritti, A.,Broccoli, V., Bonini, C., Naldini, L.2011. Site-specific integration and tailoring of cassette designfor sustainable gene transfer. Nat Methods,8(10):861-869.
Lorson, M. A., Spate, L. D., Samuel, M. S., Murphy, C. N., Lorson, C. L., Prather, R. S., Wells, K. D.2011.Disruption of the Survival Motor Neuron (SMN) gene in pigs using ssDNA. Transgenic Res,20(6):1293-1304.
Luo, Y., Bolund, L., Sorensen, C. B.2012. Pig gene knockout by rAAV-mediated homologousrecombination: comparison of BRCA1gene knockout efficiency in Yucatan and Gottingenfibroblasts with slightly different target sequences. Transgenic Res,21:671-676.
Luo, Y., Li, J., Liu, Y., Lin, L., Du, Y., Li, S., Yang, H., Vajta, G., Callesen, H., Bolund, L., Sorensen, C. B.2011. High efficiency of BRCA1knockout using rAAV-mediated gene targeting: developing a pigmodel for breast cancer. Transgenic Res,20(5):975-988.
Maeder, M. L., Thibodeau-Beganny, S., Osiak, A., Wright, D. A., Anthony, R. M., Eichtinger, M., Jiang, T.,Foley, J. E., Winfrey, R. J., Townsend, J. A., Unger-Wallace, E., Sander, J. D., Muller-Lerch, F., Fu,F., Pearlberg, J., Gobel, C., Dassile, J. P., Pruett-miller, S. M., Porteus, M. H., Sgroi, D. C.,Iafrate, A. J., Dobbs, D., McCray, P. B. Jr., Cathomen, T., Voytas, D. F., Joung, J. K.2008. Rapid"open-source" engineering of customized zinc-finger nucleases for highly efficient genemodification. Mol Cell,31(2):294-301.
Maeder, M. L., Thibodeau-Beganny, S., Sander, J. D., Voytas, D. F., Joung, J. K.2009. Oligomerized poolengineering (OPEN): an 'open-source' protocol for making customized zinc-finger arrays. NatProtoc,4(10):1471-1501.
Maga, E. A., Sargent, R. G., Zeng, H., Pati, S., Zarling, D. A., Oppenheim, S. M., Collette, N. M., Moyer, A.L., Conrad-Brink, J. S., Rowe, J. D., BonDurant, R. H., Anderson, G. B., Murray, J. D.2003.Increased efficiency of transgenic livestock production. Transgenic Res,12(4):485-496.
Maga, E. A., Shoemaker, C. F., Rowe, J. D., BonDurant, R. H., Anderson, G. B., Murray, J. D.2006.Production and processing of milk from transgenic goats expressing human lysozyme in themammary gland. J Dairy Sci,89(2):518-524.
Majumdar, A., Khorlin, A., Dyatkina, N., Lin, F. L., Powell, J., Liu, J., Fei, Z., Khripine, Y., Watanabe, K.A., George, J., Glazer, P. M., Sedman, M. M.1998. Targeted gene knockout mediated by triplehelix forming oligonucleotides. Nat Genet,20(2):212-214.
Mak, A. N., Bradley, P., Cernadas, R. A., Bogdanove, A. J., Stoddard, B. L.2012. The crystal structure ofTAL effector PthXo1bound to its DNA target. Science,335(6069):716-719.
Marcaida, M. J., Munoz, I. G., Blanco, F. J., Prieto, J., Montoya, G.2010. Homing endonucleases: frombasics to therapeutic applications. Cell Mol Life Sci,67(5):727-748.
Marques, M. M., Thomson, A. J., McCreath, K. J., McWhir, J.2006. Conventional gene targeting protocolslead to loss of targeted cells when applied to a silent gene locus in primary fibroblasts. JBiotechnol,125(2):185-193.
Martinez-Diaz, M. A., Che, L., Albornoz, M., Seneda, M. M., Collis, D., Coutinho, A. R., El-Beirouthi, N.,Laurin, D., Zhao, X., Bordignon, V.2010. Pre-and postimplantation development of swine-clonedembryos derived from fibroblasts and bone marrow cells after inhibition of histone deacetylases.Cell Reprogram,12(1):85-94.
McCreath, K. J., Howcroft, J., Campbell, K. H., Colman, A., Schnieke, A. E., Kind, A. J.2000. Productionof gene-targeted sheep by nuclear transfer from cultured somatic cells. Nature,405(6790):1066-1069.
Meehan, D. T., Zink, M. A., Mahlen, M., Nelson, M., Sanger, W. G., Mitalipov, S. M., Wolf, D. P., Ouellette,M. M., Norgren, R. B., Jr.2008. Gene targeting in adult rhesus macaque fibroblasts. BMCBiotechnol,8:31.
Mendicino, M., Ramsoondar, J., Phelps, C., Vaught, T., Ball, S., LeRoith, T., Monahan, J., Chen, S., Dandro,A., Boone, J., Jobst, P., Vance, A., Wertz, N., Bergman, Z., Sun, X. Z., Sun, X. Z., Polejaeva, I.,Butler, J., Dai, Y., Ayares, D., Wells, K.2011. Generation of antibody-and B cell-deficient pigs bytargeted disruption of the J-region gene segment of the heavy chain locus. Transgenic Res,20(3):625-641.
Meng, X., Noyes, M. B., Zhu, L. J., Lawson, N. D., Wolfe, S. A.2008. Targeted gene inactivation inzebrafish using engineered zinc-finger nucleases. Nat Biotechnol,26(6):695-701.
Meyer, M., de Angelis, M. H., Wurst, W., Kuhn, R.2010. Gene targeting by homologous recombination inmouse zygotes mediated by zinc-finger nucleases. Proc Natl Acad Sci U S A,107(34):15022-15026.
Mir, B., Piedrahita, J. A.2004. Nuclear localization signal and cell synchrony enhance gene targetingefficiency in primary fetal fibroblasts. Nucleic Acids Res,32(3):e25.
Mirkin, S. M., Lyamichev, V. I., Drushlyak, K. N., Dobrynin, V. N., Filippov, S. A., Frank-Kamenetskii, M.D.1987. DNA H form requires a homopurine-homopyrimidine mirror repeat. Nature,330(6147):495-497.
Mitsui, K., Suzuki, K., Aizawa, E., Kawase, E., Suemori, H., Nakatsuji, N., Mitani, K.2009. Gene targetingin human pluripotent stem cells with adeno-associated virus vectors. Biochem Biophys ResCommun,388(4):711-717.
Moehle, E. A., Rock, J. M., Lee, Y. L., Jouvenot, Y., DeKelver, R. C., Gregory, P. D., Urnov, F. D., Holmes,M. C.2007. Targeted gene addition into a specified location in the human genome using designedzinc finger nucleases. Proc Natl Acad Sci U S A,104(9):3055-3060.
Moisyadi, S., Kaminski, J. M., Yanagimachi, R.2009. Use of intracytoplasmic sperm injection (ICSI) togenerate transgenic animals. Comp Immunol Microb Infect Dis,32(2):47-60.
Morgan, R. D., Luyten, Y. A.2009. Rational engineering of type II restriction endonuclease DNA bindingand cleavage specificity. Nucleic Acids Res,37(15):5222-5233.
Morozov, V., Wawrousek, E. F.2008. Single-strand DNA-mediated targeted mutagenesis of genomic DNAin early mouse embryos is stimulated by Rad51/54and by Ku70/86inhibition. Gene Ther,15(6):468-472.
Morton, J., Davis, M. W., Jorgensen, E. M., Carroll, D.2006. Induction and repair of zinc-fingernuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells. Proc Natl Acad SciU S A,103(44):16370-16375.
Moscou, M. J., Bogdanove, A. J.2009. A simple cipher governs DNA recognition by TAL effectors.Science,326(5959):1501.
Moser, H. E., Dervan, P. B.1987. Sequence-specific cleavage of double helical DNA by triple helixformation. Science,238(4827):645-650.
Mountford, P., Zevnik, B., Duwel, A., Nichols, J., Li, M., Dani, C., Robertson, M., Chambers, I., Smith, A.1994. Dicistronic targeting constructs: reporters and modifiers of mammalian gene expression.Proc Natl Acad Sci U S A,91(10):4303-4307.
Nagano, M., Brinster, C. J., Orwig, K. E., Ryu, B. Y., Avarbock, M. R., Brinster, R. L.2001. Transgenicmice produced by retroviral transduction of male germ-line stem cells. Proc Natl Acad Sci U S A,98(23):13090-13095.
Nagano, M., Suita, S., Yamanouchi, T.2000. The validity of bioelectrical impedance phase angle fornutritional assessment in children. J Pediatr Surg,35(7):1035-1039.
Nagy, A.2003. Manipulating the mouse embryo: a laboratory manual: Cold Spring Harbor Laboratory Pr.
Nakayama, A., Sato, M., Shinohara, M., Matsubara, S., Yokomine, T., Akasaka, E., Yoshida, M., Takao, S.2007. Efficient Transfection of primarily cultured porcine embryonic fibroblasts using the Amaxanucleofection system (TM). Cloning Stem Cells,9(4):523-534.
Neu, J. M., White, D. J. G.2003. Conditional immortalization of fibroblasts for genetic engineering of animals.Xenotransplantation,10(5):529-529.
Niemann, H., Kues, W., Carnwath, J. W.2009. Transgenic farm animals: Current status and perspectives foragriculture and biomedicine. Genet Eng Livest,1-30.
Niemann, H., Kues, W. A.2007. Transgenic farm animals: an update. Reprod Fert Develop,19(6):762-770.
Niemann, H., Kuhla, B., Flachowsky, G.2011. Perspectives for feed-efficient animal production. J AnimSci,89(12):4344-4363.
Nottle, M. B., Beebe, L. F., Harrison, S. J., McIlfatrick, S. M., Ashman, R. J., O'Connell, P. J., Salvaris, E.J., Fisicaro, N., Pommey, S., Cowan, P. J., d’Apice, A. J.2007. Production of homozygousalpha-1,3-galactosyltransferase knockout pigs by breeding and somatic cell nuclear transfer.Xenotransplantation,14(4):339-344.
Ochiai, H., Fujita, K., Suzuki, K., Nishikawa, M., Shibata, T., Sakamoto, N., Yamamoto, T.2010. Targetedmutagenesis in the sea urchin embryo using zinc-finger nucleases. Genes Cells,15(8):875-885.
Osakabe, K., Osakabe, Y., Toki, S.2010. Site-directed mutagenesis in Arabidopsis using custom-designedzinc finger nucleases. Proc Natl Acad Sci U S A,107(26):12034-12039.
Osborn, M. J., DeFeo, A. P., Blazar, B. R., Tolar, J.2011. Synthetic zinc finger nuclease design and rapidassembly. Hum Gene Ther,22(9):1155-1165.
Pan, D. K., Zhang, L., Zhou, Y. R., Feng, C., Long, C., Liu, X., Wan, R., Zhang, J., Lin, A. X., Dong, E. Q.,Wang, S. C., Xu, H. G., Chen, H. X.2010. Efficient production of omega-3fatty acid desaturase(sFat-1)-transgenic pigs by somatic cell nuclear transfer. Science China-Life Sciences,53(4):517-523.
Paques, F., Duchateau, P.2007. Meganucleases and DNA double-strand break-induced recombination:perspectives for gene therapy. Curr Gene Ther,7(1):49-66.
Park, J. K., Lee, Y. K., Lee, P., Chung, H. J., Kim, S., Lee, H. G., Seo, M. K., Han, J. H., Park, C. G., Kim,H. T., Kim, Y. K., Min, K. S., Kim, J. H., Lee, H. T., Chang, W. K.2006. Recombinant humanerythropoietin produced in milk of transgenic pigs. J Biotechnol,122(3):362-371.
Park, J. Y., Kim, J. H., Choi, Y. J., Hwang, K. C., Cho, S. K., Park, H. H., Paik, S. S., Kim, T., Park, C., Lee,H. T., Seo, H. G., Park, S. B., Hwang, S.2009. Comparative proteomic analysis of malformedumbilical cords from somatic cell nuclear transfer-derived piglets: implications for early postnataldeath. BMC Genomics,10:511.
Pattanayak, V., Ramirez, C. L., Joung, J. K., Liu, D. R.2011. Revealing off-target cleavage specificities ofzinc-finger nucleases by in vitro selection. Nat Methods,8(9):765-770.
Paulk, N. K., Marquez Loza, L., Finegold, M., Grompe, M.2012. AAV-mediated gene targeting issignificantly enhance by transient inhibition of NHEJ or the proteasome in vivo. Hum Gene Ther,in press, doi:10.1089/hum.2012.038.
Pavletich, N. P., Pabo, C. O.1991. Zinc finger-DNA recognition: crystal structure of a Zif268-DNAcomplex at2.1A. Science,252(5007):809-817.
Perry, A. C., Wakayama, T., Kishikawa, H., Kasai, T., Okabe, M., Toyoda, Y., Yanagimachi, R.1999.Mammalian transgenesis by intracytoplasmic sperm injection. Science,284(5417):1180-1183.
Peura, T. T., Vajta, G.2003. A comparison of established and new approaches in ovine and bovine nucleartransfer. Cloning Stem Cells,5(4):257-277.
Phelps, C. J., Koike, C., Vaught, T. D., Boone, J., Wells, K. D., Chen, S. H., Ball, S., Specht, S. M.,Polejaeva, I. A., Monahan, J. A., Jobst, P. M., Sharma, S. B., Lamborn, A. E., Garst, A. S., Moore,M., Demetris, A. J., Rudert, W. A., Bottino, R., Bertera, S., Trucco, M., Starzl, T. E., Dai, Y.,Ayares, D. L.2003. Production of alpha1,3-galactosyltransferase-deficient pigs. Science,299(5605):411-414.
Pingoud, A., Wende, W.2011. Generation of novel nucleases with extended specificity by rational andcombinatorial strategies. ChemBioChem,12(10):1495-1500.
Polejaeva, I. A., Chen, S. H., Vaught, T. D., Page, R. L., Mullins, J., Ball, S., Dai, Y., Boone, J., Walker, S.,Ayares, D. L., Colman, A., Campbell, K. H.2000. Cloned pigs produced by nuclear transfer fromadult somatic cells. Nature,407(6800):86-90.
Ramachandra, C. J., Shahbazi, M., Kwang, T. W., Choudhury, Y., Bak, X. Y., Yang, J., Wang, S.2011.Efficient recombinase-mediated cassette exchange at the AAVS1locus in human embryonic stemcells using baculoviral vectors. Nucleic Acids Res,39(16):e107.
Ramsoondar, J., Mendicino, M., Phelps, C., Vaught, T., Ball, S., Monahan, J., Chen, S., Dandro, A., Boone,J., Jobst, P., Vance, A., Wertz, N., Polejaeva, I., Butler, J., Dai, Y., Ayares, D., Wells, K.2011.Targeted disruption of the porcine immunoglobulin kappa light chain locus. Transgenic Res,20(3):643-653.
Reh, W. A., Maga, E. A., Collette, N. M. B., Moyer, A., Conrad-Brink, J. S., Taylor, S. J., DePeters, E. J.,Oppenheim, S., Rowe, J. D., BonDurant, R. H., Anderson, G. B., Murray, J. D.2004. Hot topic:Using a stearoyl-CoA desaturase transgene to alter milk fatty acid composition. J Dairy Sci,87(10):3510-3514.
Ren, H. Y., Zheng, X. M., Chen, H. X., Li, K.2011a. Transgenic Pigs Carrying a Synthesized Fatty AcidDesaturase Gene Yield High Level of omega-3PUFAs. Agricultural Sciences in China,10(10):1603-1608.
Ren, J., Pak, Y., He, L., Qian, L., Gu, Y., Li, H., Rao, L., Liao, J., Cui, C., Xu, X., Zhou, J., Ri, H., Xiao, L.2011b. Generation of hircine-induced pluripotent stem cells by somatic cell reprogramming. CellRes,21(5):849-853.
Reyon, D., Tsai, S. Q., Khayter, C., Foden, J. A., Sander, J. D., Joung, J. K.2012. FLASH assembly ofTALENs for high-throughput genome editing. Nat Biotechnol,30(5):460-465.
Richt, J. A., Kasinathan, P., Hamir, A. N., Castilla, J., Sathiyaseelan, T., Vargas, F., Sathiyaseelan, J., Wu, H.,Matsushita, H., Koster, J., Kato, S., Ishida, I., Soto, C., Robl, J. M., Kuroiwa, Y.2007.Production of cattle lacking prion protein. Nat Biotechnol,25(1):132-138.
Rimseliene, R., Maneliene, Z., Lubys, A., Janulaitis, A.2003. Engineering of restriction endonucleases:using methylation activity of the bifunctional endonuclease Eco57I to select the mutant with anovel sequence specificity. J Mol Biol,327(2):383-391.
Robertson, E., Bradley, A., Kuehn, M., Evans, M.1986. Germ-line transmission of genes introduced intocultured pluripotential cells by retroviral vector. Nature,323(6087):445-448.
Rogers, C. S., Hao, Y., Rokhlina, T., Samuel, M., Stoltz, D. A., Li, Y., Petroff, E., Vermeer, D. W., Kabel, A.C., Yan, Z. Spate, L., Wax, D., Murphy, C. N., Rieke, A., Whitworth, K., Linville, M. L., Korte, S.W., Engelhardt, J. F., Welsh, M. J., Prather, R. S.2008. Production of CFTR-null andCFTR-DeltaF508heterozygous pigs by adeno-associated virus-mediated gene targeting andsomatic cell nuclear transfer. J Clin Invest,118(4):1571-1577.
Romer, P., Hahn, S., Jordan, T., Strauss, T., Bonas, U., Lahaye, T.2007. Plant pathogen recognitionmediated by promoter activation of the pepper Bs3resistance gene. Science,318(5850):645-648.
Rosen, L. E., Morrison, H. A., Masri, S., Brown, M. J., Springstubb, B., Sussman, D., Stoddard, B. L.,Seligman, L. M.2006. Homing endonuclease I-CreI derivatives with novel DNA targetspecificities. Nucleic Acids Res,34(17):4791-4800.
Ross, J. W., Whyte, J. J., Zhao, J., Samuel, M., Wells, K. D., Prather, R. S.2010. Optimization ofsquare-wave electroporation for transfection of porcine fetal fibroblasts. Transgenic Res,19(4):611-620.
Rossi, J., Friedmann, T.2007. Gene Transfer: Delivery and Expression of DNA and RNA, A LaboratoryManual: Cold Spring Harbor Laboratory Press.
Rouet, P., Smih, F., Jasin, M.1994. Introduction of double-strand breaks into the genome of mouse cells byexpression of a rare-cutting endonuclease. Mol Cell Biol,14(12):8096-8106.
Saito, S., Sawai, K., Ugai, H., Moriyasu, S., Minamihashi, A., Yamamoto, Y., Hirayama, H., Kageyama, S.,Pan, J. Z., Murata, T. Kobayashi, Y., Obata, Y., Yokoyama, K. K.2003. Generation of clonedcalves and transgenic chimeric embryos from bovine embryonic stem-like cells. Biochem BiophysRes Commun,309(1):104-113.
Samuels, Y., Diaz, L. A., Jr., Schmidt-Kittler, O., Cummins, J. M., Delong, L., Cheong, I., Rago, C., Huso,D. L., Lengauer, C., Kinzler, K. W., Vogelstein, B., Velculescu, V. E.2005. Mutant PIK3CApromotes cell growth and invasion of human cancer cells. Cancer Cell,7(6):561-573.
Sanchez, O., Toledo, J. R., Rodriguez, M. P., Castro, F. O.2004. Adenoviral vector mediates highexpression levels of human growth hormone in the milk of mice and goats. J Biotechnol,114(1-2):89-97.
Sander, J. D., Dahlborg, E. J., Goodwin, M. J., Cade, L., Zhang, F., Cifuentes, D., Curtin, S. J., Blackburn, J.S., Thibodeau-Beganny, S., Qi, Y., Pierick, C. J., Hoffman, E., Maeder, M. L., Khayter, C., Reyon,D., Dobbs, D., Langenau, D. M., Stupar, R. M., Giraldez, A. J., voytas, D. F., Peterson, R. T., Yeh,J. R., Joung, J. K.2011. Selection-free zinc-finger-nuclease engineering by context-dependentassembly (CoDA). Nat Methods,8(1):67-69.
Sander, J. D., Zaback, P., Joung, J. K., Voytas, D. F., Dobbs, D.2007. Zinc Finger Targeter (ZiFiT): anengineered zinc finger/target site design tool. Nucleic Acids Res,35(Web Server issue):W599-W605.
Schnieke, A. E., Kind, A. J., Ritchie, W. A., Mycock, K., Scott, A. R., Ritchie, M., Wilmut, I., Colman, A.,Campbell, K. H.1997. Human factor Ⅸ transgenic sheep produced by transfer of nuclei fromtransfected fetal fibroblasts. Science,278(5346):2130-2133.
Sebastiano, V., Maeder, M. L., Angstman, J. F., Haddad, B., Khayter, C., Yeo, D. T., Goodwin, M. J.,Hawkins, J. S., Ramirez, C. L., Batista, L. F., Artandi, S. E., Wernig. M., Joung, J. K.2011. In situgenetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells usingengineered zinc finger nucleases. Stem Cells,29(11):1717-1726.
Sedivy, J. M., Dutriaux, A.1999. Gene targeting and somatic cell genetics--a rebirth or a coming of age?Trends Genet,15(3):88-90.
Segal, D. J., Dreier, B., Beerli, R. R., Barbas, C. F.,3rd.1999. Toward controlling gene expression at will:selection and design of zinc finger domains recognizing each of the5'-GNN-3' DNA targetsequences. Proc Natl Acad Sci U S A,96(6):2758-2763.
Sendai, Y., Sawada, T., Urakawa, M., Shinkai, Y., Kubota, K., Hoshi, H., Aoyagi, Y.2006.alpha1,3-Galactosyltransferase-gene knockout in cattle using a single targeting vector with loxPsequences and cre-expressing adenovirus. Transplantation,81(5):760-766.
Shah, R. A., George, A., Singh, M. K., Kumar, D., Anand, T., Chauhan, M. S., Manik, R. S., Palta, P.,Singla, S. K.2009. Pregnancies established from handmade cloned blastocysts reconstructed usingskin fibroblasts in buffalo (Bubalus bubalis). Theriogenology,71(8):1215-1219.
Shen, W., Lan, G., Yang, X., Li, L., Min, L., Yang, Z., Tian, L., Wu, X., Sun, Y., Chen, H., Tan, J., Deng, J.,Pan, Q.2007. Targeting the exogenous htPAm gene on goat somatic cell beta-casein locus fortransgenic goat production. Mol Reprod Dev,74(4):428-434.
Shi, L. H., Ai, J. S., OuYang, Y. C., Huang, J. C., Lei, Z. L., Wang, Q., Yin, S., Han, Z. M., Sun, Q. Y., Chen,D. Y.2008. Trichostatin A and nuclear reprogramming of cloned rabbit embryos. J Anim Sci,86(5):1106-1113.
Shimizu, Y., Bhakta, M. S., Segal, D. J.2009. Restricted spacer tolerance of a zinc finger nuclease with asix amino acid linker. Bioorg Med Chem Lett,19(14):3970-3972.
Shin, T., Kraemer, D., Pryor, J., Liu, L., Rugila, J., Howe, L., Buck, S., Murphy, K., Lyons, L., Westhusin,M.2002. A cat cloned by nuclear transplantation. Nature,415(6874):859.
Shukla, V. K., Doyon, Y., Miller, J. C., DeKelver, R. C., Moehle, E. A., Worden, S. E., Mitchell, J. C.,Arnold, N. L., Gopalan, S., Meng, X., Choi, V. M., Rock, J. M., Wu, Y. Y., Katibah, G. E., Zhifang,G., McCaskill, D., Simpson, M. A., Blakeslee, B., Greenwalt, S. A., Butler, H. J., Hinkley, S. J.,Zhang, L., Rebar, E. J., Gregory, P. D., Urnov, F. D.2009. Precise genome modification in the cropspecies Zea mays using zinc-finger nucleases. Nature,459(7245):437-441.
Simon, P., Cannata, F., Concordet, J. P., Giovannangeli, C.2008. Targeting DNA with triplex-formingoligonucleotides to modify gene sequence. Biochimie,90(8):1109-1116.
Smih, F., Rouet, P., Romanienko, P. J., Jasin, M.1995. Double-strand breaks at the target locus stimulategene targeting in embryonic stem cells. Nucleic Acids Res,23(24):5012-5019.
Smith, J., Bibikova, M., Whitby, F. G., Reddy, A. R., Chandrasegaran, S., Carroll, D.2000. Requirementsfor double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognitiondomains. Nucleic Acids Res,28(17):3361-3369.
Soldner, F., Laganiere, J., Cheng, A. W., Hockemeyer, D., Gao, Q., Alagappan, R., Khurana, V., Golbe, L. I.,Myers, R. H., Lindquist, S., Zhang, L., Guschin, D., Fong, L. K., Vu, B. J., Meng, X. D., Urnov, F.D., Rebar, E. J., Gregory, P. D., Zhang, H. S., Jaenisch, R.2011. Generation of isogenic pluripotentstem Cells differing Exclusively at two early onset parkinson point mutations. Cell,146(2):318-331.
Spencer, W. J., Binette, A., Ward, T. L., Davis, L. D., Blais, D. R., Harrold, J., Mack, D. R., Altosaar, I.2010. Alpha-lactalbumin in human milk alters the proteolytic degradation of soluble CD14byforming a complex. Pediatr Res,68(6):490-493.
Stadtfeld, M., Hochedlinger, K.2010. Induced pluripotency: history, mechanisms, and applications. GenesDev,24(20):2239-2263.
Stinnakre, M. G., Soulier, S., Schibler, L., Lepourry, L., Mercier, J. C., Vilotte, J. L.1999.Position-independent and copy-number-related expression of a goat bacterial artificialchromosome alpha-lactalbumin gene in transgenic mice. Biochem J,339:33-36.
Stoddard, B. L.2011. Homing endonucleases: from microbial genetic invaders to reagents for targetedDNA modification. Structure,19(1):7-15.
Sun, X., Yan, Z., Yi, Y., Li, Z., Lei, D., Rogers, C. S., Chen, J., Zhang, Y., Welsh, M. J., Leno, G. H.,Engelhardt, J. F.2008. Adeno-associated virus-targeted disruption of the CFTR gene in clonedferrets. J Clin Invest,118(4):1578-1583.
Svensson, K., Mattsson, R., James, T. C., Wentzel, P., Pilartz, M., MacLaughlin, J., Miller, S. J., Olsson, T.,Eriksson, U. J., Ohlsson, R.1998. The paternal allele of the H19gene is progressively silencedduring early mouse development: the acetylation status of histones may be involved in thegeneration of variegated expression patterns. Development,125(1):61-69.
Svensson, M., Hakansson, A., Mossberg, A. K., Linse, S., Svanborg, C.2000. Conversion ofalpha-lactalbumin to a protein inducing apoptosis. Proc Natl Acad Sci U S A,97(8):4221-4426.
Szostak, J. W., Orr-Weaver, T. L., Rothstein, R. J., Stahl, F. W.1983. The double-strand-break repair modelfor recombination. Cell,33(1):25-35.
Tachibana, M., Sparman, M., Ramsey, C., Ma, H., Lee, H. S., Penedo, M. C., Mitalipov, S.2012.Generation of chimeric rhesus monkeys. Cell,148(1-2):285-295.
Takahagi, Y., Fujimura, T., Miyagawa, S., Nagashima, H., Shigehisa, T., Shirakura, R., Murakami, H.2005.Production of alpha1,3-galactosyltransferase gene knockout pigs expressing both humandecay-accelerating factor and N-acetylglucosaminyltransferase III. Mol Reprod Dev,71(3):331-338.
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., Yamanaka, S.2007. Inductionof pluripotent stem cells from adult human fibroblasts by defined factors. Cell,131(5):861-872.
Takahashi, K., Yamanaka, S.2006. Induction of pluripotent stem cells from mouse embryonic and adultfibroblast cultures by defined factors. Cell,126(4):663-676.
Takasu, Y., Kobayashi, I., Beumer, K., Uchino, K., Sezutsu, H., Sajwan, S., Carroll, D., Tamura, T.,Zurovec, M.2010. Targeted mutagenesis in the silkworm Bombyx mori using zinc finger nucleasemRNA injection. Insect Biochem Mol Biol,40(10):759-765.
te Riele, H., Maandag, E. R., Berns, A.1992. Highly efficient gene targeting in embryonic stem cellsthrough homologous recombination with isogenic DNA constructs. Proc Natl Acad Sci U S A,89(11):5128-5132.
Thomas, K. R., Capecchi, M. R.1987. Site-directed mutagenesis by gene targeting in mouseembryo-derived stem cells. Cell,51(3):503-512.
Thomas, K. R., Folger, K. R., Capecchi, M. R.1986. High frequency targeting of genes to specific sites inthe mammalian genome. Cell,44(3):419-428.
Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., Jones, J.M.1998. Embryonic stem cell lines derived from human blastocysts. Science,282(5391):1145-1147.
Toledo, J. R., Sanchez, O., Segui, R. M., Garcia, G., Montanez, M., Zamora, P. A., Rodriguez, M. P.,Cremata, J. A.2006. High expression level of recombinant human erythropoietin in the milk ofnon-transgenic goats. J Biotechnol,123(2):225-235.
Tomioka, I., Maeda, T., Shimada, H., Kawai, K., Okada, Y., Igarashi, H., Oiwa, R., Iwasaki, T., Aoki, M.,Kimura, T., Shiozawa, S., Shinohara, H., Suemizu, H., Sasaki, E., Okano, H.2010. Generatinginduced pluripotent stem cells from common marmoset (Callithrix jacchus) fetal liver cells usingdefined factors, including Lin28. Genes Cells,15(9):959-969.
Tong, C., Li, P., Wu, N. L., Yan, Y., Ying, Q. L.2010. Production of p53gene knockout rats by homologousrecombination in embryonic stem cells. Nature,467(7312):211-213.
Tong, J., Wei, H. X., Liu, X. F., Hu, W. P., Bi, M. J., Wang, Y. Y., Li, Q. Y., Li, N.2011. Production ofrecombinant human lysozyme in the milk of transgenic pigs. Transgenic Res,20(2):417-419.
Townsend, J. A., Wright, D. A., Winfrey, R. J., Fu, F., Maeder, M. L., Joung, J. K., Voytas, D. F.2009.High-frequency modification of plant genes using engineered zinc-finger nucleases. Nature,459(7245):442-445.
Tsai, T. L., Shieh, D. B., Yeh, C. S., Tzeng, Y., Htet, K., Chuang, K. S., Hwu, J. R., Su, W. C.2010. Thedown regulation of target genes by photo activated DNA nanoscissors. Biomaterials,31(25):6545-6554.
Tsuji, Y., Kato, Y., Tsunoda, Y.2009. The developmental potential of mouse somatic cellnuclear-transferred oocytes treated with trichostatin A and5-aza-2'-deoxycytidine. Zygote,17(2):109-115.
Umeyama, K., Saito, H., Kurome, M., Matsunari, H., Watanabe, M., Nakauchi, H., Nagashima, H.2012.Characterization of the ICSI-mediated gene transfer method in the production of transgenic pigs.Mol Reprod Dev,79(3):218-228.
Ushida, Y., Shimokawa, Y., Toida, T., Matsui, H., Takase, M.2007. Bovine alpha-lactalbumin stimulatesmucus metabolism in gastric mucosa. J Dairy Sci,90(2):541-546.
Vajta, G., Callesen, H.2012. Establishment of an efficient somatic cell nuclear transfer system forproduction of transgenic pigs. Theriogenology,77(7):1263-1274.
Vajta, G., Lewis, I. M., Trounson, A. O., Purup, S., Maddox-Hyttel, P., Schmidt, M., Pedersen, H. G., Greve,T., Callesen, H.2003. Handmade somatic cell cloning in cattle: analysis of factors contributing tohigh efficiency in vitro. Biol Reprod,68(2):571-578.
Valls, E., Sanchez-Molina, S., Martinez-Balbas, M. A.2005. Role of histone modifications in marking andactivating genes through mitosis. J Biol Chem,280(52):42592-42600.
van Berkel, P. H. C., Welling, M. M., Geerts, M., van Veen, H. A., Ravensbergen, B., Salaheddine, M.,Pauwels, E. K. J., Pieper, F., Nuijens, J. H., Nibbering, P. H.2002. Large scale production ofrecombinant human lactoferrin in the milk of transgenic cows. Nat Biotechnol,20(5):484-487.
Vanamee, E. S., Berriman, J., Aggarwal, A. K.2007. An EM view of the FokI synaptic complex by singleparticle analysis. J Mol Biol,370(2):207-212.
Vanamee, E. S., Santagata, S., Aggarwal, A. K.2001. FokI requires two specific DNA sites for cleavage. JMol Biol,309(1):69-78.
Vasquez, K. M., Marburger, K., Intody, Z., Wilson, J. H.2001. Manipulating the mammalian genome byhomologous recombination. Proc Natl Acad Sci U S A,98(15):8403-8410.
Wakayama, T., Perry, A. C., Zuccotti, M., Johnson, K. R., Yanagimachi, R.1998. Full-term development ofmice from enucleated oocytes injected with cumulus cell nuclei. Nature,394(6691):369-374.
Waldman, A. S., Liskay, R. M.1988. Dependence of intrachromosomal recombination in mammalian cellson uninterrupted homology. Mol Cell Biol,8(12):5350-5357.
Wang, J., Friedman, G., Doyon, Y., Wang, N. S., Li, C. J., Miller, J. C., Hua, K. L., Yan, J. J., Babiarz, J. E.,Gregory, P. D., Holmes, M. C.2012. Targeted gene addition to a predetermined site in the humangenome using a ZFN-based nicking enzyme. Genome Res, in press, doi:10.1101/gr.122879.111.
Wang, J., Yang, P., Tang, B., Sun, X., Zhang, R., Guo, C., Gong, G., Liu, Y., Li, R., Zhang, L., Dai, Y., Li,N.2008. Expression and Characterization of Bioactive Recombinant Human alpha-Lactalbumin inthe Milk of Transgenic Cloned Cows. J Dairy Sci,91(12):4466-4476.
Wang, S., Sun, X., Ding, F., Zhang, K., Zhao, R., Li, S., Li, R., Tang, B., Zhang, L., Liu, Y., Li, J., Gao, F.,Wang, H., Wang, L., Dai, Y., Li, N.2009. Removal of selectable marker gene from fibroblast cellsin transgenic cloned cattle by transient expression of Cre recombinase and subsequent effects onrecloned embryo development. Theriogenology,72(4):535-541.
Wang, Y. S., Xiong, X. R., An, Z. X., Wang, L. J., Liu, J., Quan, F. S., Hua, S., Zhang, Y.2011. Productionof cloned calves by combination treatment of both donor cells and early cloned embryos with5-aza-2'-deoxycytidine and trichostatin A. Theriogenology,75(5):819-825.
Wani, N. A., Wernery, U., Hassan, F. A., Wernery, R., Skidmore, J. A.2010. Production of the first clonedcamel by somatic cell nuclear transfer. Biol Reprod,82(2):373-379.
Watanabe, M., Kurome, M., Matsunari, H., Nakano, K., Umeyema, K., Shiota, A., Nakauchi, H.,Nagashima, H.2012. The creation of transgenic pigs expressing human proteins usingBAC-derived, full-length genes and intracytoplasmic sperm injection-mediated gene transfer.Transgenic Res,21(3):605-618.
Watanabe, M., Umeyama, K., Matsunari, H., Takayanagi, S., Haruyama, E., Nakano, K., Fujiwara, T.,Ikezawa, Y., Nakauchi, H., Nagashima, H.2010. Knockout of exogenous EGFP gene in porcinesomatic cells using zinc-finger nucleases. Biochem Biophys Res Commun,402(1):14-18.
West, F. D., Uhl, E. W., Liu, Y., Stowe, H., Lu, Y., Yu, P., Gallegos-Cardenas, A., Pratt, S. L., Stice, S. L.2011. Brief report: chimeric pigs produced from induced pluripotent stem cells demonstrategermline transmission and no evidence of tumor formation in young pigs. Stem Cells,29(10):1640-1643.
Whitelaw, C. B., Harris, S., McClenaghan, M., Simons, J. P., Clark, A. J.1992. Position-independentexpression of the ovine beta-lactoglobulin gene in transgenic mice. Biochem J,286(1):31-39.
Whitelaw, C. B., Lillico, S. G., King, T.2008. Production of transgenic farm animals by viralvector-mediated gene transfer. Reprod Domest Anim,43(Suppl):2355-2358.
Whyte, J. J., Zhao, J. G., Wells, K. D., Samuel, M. S., Whitworth, K. M., Walters, E. M., Laughlin, M. H.,Prather, R. S.2011. Gene Targeting With Zinc Finger Nucleases to Produce Cloned eGFPKnockout Pigs. Mol Reprod Dev,78(1):2.
Williams, S. H., Sahota, V., Palmai-Pallag, T., Tebbutt, S. J., Walker, J., Harris, A.2003. Evaluation of genetargeting by homologous recombination in ovine somatic cells. Mol Reprod Dev,66(2):115-125.
Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J., Campbell, K. H.1997. Viable offspring derived fromfetal and adult mammalian cells. Nature,385(6619):810-813.
Wilson, G. L., Dean, B. S., Wang, G., Dean, D. A.1999. Nuclear import of plasmid DNA indigitonin-permeabilized cells requires both cytoplasmic factors and specific DNA sequences. JBiol Chem,274(31):22025-22032.
Wood, A. J., Lo, T. W., Zeitler, B., Pickle, C. S., Ralston, E. J., Lee, A. H., Amora, R., Miller, J. C., Leung,E., Meng, X., Zhang, L., Rebar, E. J., Gregory, P. D., Urnov, F. D., Meyer, B. J.2011. Targetedgenome editing across species using ZFNs and TALENs. Science,333(6040):307.
Woods, G. L., White, K. L., Vanderwall, D. K., Li, G. P., Aston, K. I., Bunch, T. D., Meerdo, L. N., Pate, B.J.2003. A mule cloned from fetal cells by nuclear transfer. Science,301(5636):1063.
Wright, G., Carver, A., Cottom, D., Reeves, D., Scott, A., Simons, P., Wilmut, I., Garner, I., Colman, A.1991. High level expression of active human alpha-1-antitrypsin in the milk of transgenic sheep.Biotechnol (N Y),9(9):830-834.
Wu, Q., Gaddis, S. S., MacLeod, M. C., Walborg, E. F., Thames, H. D., DiGiovanni, J., Vasquez, K. M.2007. High-affinity triplex-forming oligonucleotide target sequences in mammalian genomes. MolCarcinog,46(1):15-23.
Wu, Y., Zhang, G., Xiong, Q., Luo, F., Cui, C., Hu, W., Yu, Y., Su, J., Xu, A., Zhu, Z.2006. Integration ofdouble-fluorescence expression vectors into zebrafish genome for the selection of site-directedknockout/knockin. Mar Biotechnol (NY),8(3):304-311.
Wu, Y., Zhang, Y., Mishra, A., Tardif, S. D., Hornsby, P. J.2010. Generation of induced pluripotent stemcells from newborn marmoset skin fibroblasts. Stem Cell Res,4(3):180-188.
Wu, Z., Chen, J., Ren, J., Bao, L., Liao, J., Cui, C., Rao, L., Li, H., Gu, Y., Dai, H., Zhu, H., Teng, X.,Cheng, L., Xiao, L.2009. Generation of pig induced pluripotent stem cells with a drug-induciblesystem. J Mol Cell Biol,1(1):46-54.
Yang, B., Wang, J., Tang, B., Liu, Y., Guo, C., Yang, P., Yu, T., Li, R., Zhao, J., Zhang, L., Dai, Y., Li, N.2011a. Characterization of bioactive recombinant human lysozyme expressed in milk of clonedtransgenic cattle. PLoS One,6(3):e17593.
Yang, D., Yang, H., Li, W., Zhao, B., Ouyang, Z., Liu, Z., Zhao, Y., Fan, N., Song, J., Tian, J., Li, F., Zhang,J., Chang, L., Pei, D., Chen, Y. E., Lai, L.2011b. Generation of PPARgamma mono-allelicknockout pigs via zinc-finger nucleases and nuclear transfer cloning. Cell Res,21(6):979-982.
Yang, H., Shi, L., Wang, B. A., Liang, D., Zhong, C., Liu, W., Nie, Y., Liu, J., Zhao, J., Gao, X., Li, D., Xu,G. L., Li, J.2012. Generation of genetically modified mice by oocyte injection of androgenetichaploid embryonic stem cells. Cell,149(3):605-617.
Yang, P., Wang, J., Gong, G., Sun, X., Zhang, R., Du, Z., Liu, Y., Li, R., Ding, F., Tang, B., Dai, Y., Li, N.2008. Cattle mammary bioreactor generated by a novel procedure of transgenic cloning forlarge-scale production of functional human lactoferrin. PLoS One,3(10):e3453.
Yoshikawa, S., Kawakami, K., Zhao, X. C.2008. G2R Cre reporter transgenic zebrafish. Dev Dyn,237(9):2460-2465.
Yu, G., Chen, J., Xu, Y., Zhu, C., Yu, H., Liu, S., Sha, H., Xu, X., Wu, Y., Zhang, A., Ma, J., Cheng, G.2009.Generation of goats lacking prion protein. Mol Reprod Dev,76(1):3.
Yu, G., Chen, J., Yu, H., Liu, S., Xu, X., Sha, H., Zhang, X., Wu, G., Xu, S., Cheng, G.2006. Functionaldisruption of the prion protein gene in cloned goats. J Gen Virol,87(4):1019-1027.
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir,G. A., Ruotti, V., Stewart, R.Slukvin, II. Thomson, J. A.2007. Induced pluripotent stem cell linesderived from human somatic cells. Science,318(5858):1917-1920.
Yu, S., Luo, J., Song, Z., Ding, F., Dai, Y., Li, N.2011a. Highly efficient modification of beta-lactoglobulin(BLG) gene via zinc-finger nucleases in cattle. Cell Res,21(11):1638-1640.
Yu, T. A., Guo, C. D., Wang, J. W., Hao, P. L., Sui, S. C., Chen, X. P., Zhang, R., Wang, P. P., Yu, G. L.,Zhang, L., Dai, Y. P., Li, N.2011b. Comprehensive characterization of the site-specificN-glycosylation of wild-type and recombinant human lactoferrin expressed in the milk oftransgenic cloned cattle. Glycobiology,21(2):206-224.
Zeng, W., Tang, L., Bondareva, A., Luo, J., Megee, S. O., Modelski, M., Blash, S., Melican, D. T.,Destrempes, M. M., Overton, S. A., Gavin, W. G., Ayres, S., Echelard, Y., Dobrinski, I.2012.Non-viral transfection of goat germline stem cells by nucleofection results in production oftransgenic sperm after germ cell transplantation. Mol Reprod Dev,79(4):255-261.
Zhang, A. L., Zhang, L., Zhang, L. Z., Chen, H., Lan, X. Y., Zhang, C. L., Zhang, C. F.2010a. An efficientand rapid method for gene cloning from eukaryotic genomic DNA using overlap-PCR: With anexample of cattle Ghrelin gene. Biochem Biophys Res Commun,391(3):1490-1493.
Zhang, F., Maeder, M. L., Unger-Wallace, E., Hoshaw, J. P., Reyon, D., Christian, M., Li, X., Pierick, C. J.,Dobbs, D., Peterson, T., Joung, J. K., Voytas, D. F.2010b. High frequency targeted mutagenesis inArabidopsis thaliana using zinc finger nucleases. Proc Natl Acad Sci U S A,107(26):12028-12033.
Zhang, L., Yang, X., An, X., Chen, Y.2007. Myostatin gene targeting in cultured China Han ovinemyoblast cells. Animal,1(10):1401-1408.
Zhang, Y., Yang, Z. J., Yang, Y. Z., Wang, S. Z., Shi, L. J., Xie, W. H., Sun, K. J., Zou, K., Wang, L., Xiong,J., Xiang, J., Wu, J.2011. Production of transgenic mice by random recombination of targetedgenes in female germline stem cells. J Mol Cell Biol,3(2):132-141.
Zhao, J., Ross, J. W., Hao, Y., Spate, L. D., Walters, E. M., Samuel, M. S., Rieke, A., Murphy, C. N.,Prather, R. S.2009a. Significant improvement in cloning efficiency of an inbred miniature pig byhistone deacetylase inhibitor treatment after somatic cell nuclear transfer. Biol Reprod,81(3):525-530.
Zhao, J. G., Hao, Y. H., Ross, J. W., Spate, L. D., Walters, E. M., Samuel, M. S., Rieke, A., Murphy, C. N.,Prather, R. S.2010. Histone deacetylase inhibitors improve in vitro and in vivo developmentalcompetence of somatic cell nuclear transfer porcine embryos. Cell Reprogram,12(1):75-83.
Zhao, X. Y., Li, W., Lv, Z., Liu, L., Tong, M., Hai, T., Hao, J., Guo, C. L., Ma, Q. W., Wang, L., Zeng, F.,Zhou, Q.2009b. iPS cells produce viable mice through tetraploid complementation. Nature,461(7260):86-90.
Zhao, Y. J., Yu, M. J., Wang, L. B., Li, Y. F., Fan, J. S., Yang, Q., Jin, Y. P.2012. Spontaneous uptake ofexogenous DNA by goat spermatozoa and selection of donor bucks for sperm-mediated genetransfer. Mol Biol Rep,39(3):2659-2664.
Zheng, Y. L., Ma, H. M., Zheng, Y. M., Wang, Y. S., Zhang, B. W., He, X. Y., He, X. N., Liu, J., Zhang, Y.2011. Site-directed mutagenesis of the myostatin gene in ovine fetal myoblast cells in vitro. ResVet Sci, in press, doi:10.1016/j.rvsc.2011.10.022.
Zhou, H., Wu, S., Joo, J. Y., Zhu, S., Han, D. W., Lin, T., Trauger, S., Bien, G., Yao, S., Zhu, Y., Siuzdak, G.,Sch ler, H. R., Duan, L., Ding, S.2009. Generation of induced pluripotent stem cells usingrecombinant proteins. Cell Stem Cell,4(5):381-384.
Zhou, Q., Renard, J. P., Le Friec, G., Brochard, V., Beaujean, N., Cherifi, Y., Fraichard, A., Cozzi, J.2003.Generation of fertile cloned rats by regulating oocyte activation. Science,302(5648):1179.
Zhu, C., Li, B., Yu, G., Chen, J., Yu, H., Xu, X., Wu, Y., Zhang, A., Cheng, G.2009. Production of Prnp-/-goats by gene targeting in adult fibroblasts. Transgenic Res,18(2):163-171.
Zlatanova, J., Caiafa, P., Van Holde, K.2000. Linker histone binding and displacement: versatilemechanism for transcriptional regulation. FASEB J,14(12):1697-1704.
Zou, K., Yuan, Z., Yang, Z., Luo, H., Sun, K., Zhou, L., Xiang, J., Shi, L., Yu, Q., Zhang, Y., Hou, R. Wu. J.
2009. Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat
Cell Biol,11(5):631-636.