Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Originally published in Science Express on 3 January 2002
Science 8 February 2002:
Vol. 295. no. 5557, pp. 1089 - 1092
DOI: 10.1126/science.1068228
Prev | Table of Contents

Reports

Production of alpha -1,3-Galactosyltransferase Knockout Pigs by Nuclear Transfer Cloning

Liangxue Lai,1 Donna Kolber-Simonds,3 Kwang-Wook Park,1 Hee-Tae Cheong,14 Julia L. Greenstein,3 Gi-Sun Im,15 Melissa Samuel,1 Aaron Bonk,1 August Rieke,1 Billy N. Day,1 Clifton N. Murphy,1 David B. Carter,12 Robert J. Hawley,3 Randall S. Prather1*

The presence of galactose alpha -1,3-galactose residues on the surface of pig cells is a major obstacle to successful xenotransplantation. Here, we report the production of four live pigs in which one allele of the alpha -1,3-galactosyltransferase locus has been knocked out. These pigs were produced by nuclear transfer technology; clonal fetal fibroblast cell lines were used as nuclear donors for embryos reconstructed with enucleated pig oocytes.

1 Department of Animal Science,
2 Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
3 Immerge BioTherapeutics Inc., Charlestown, MA 02129, USA.
4 Department of Veterinary Medicine, College of Animal Resource Science, Kangwon National University, Chunchon 200-701, Korea.
5 National Livestock Research Institute, Suwon 441-350, Korea.
*   To whom correspondence should be addressed. E-mail: pratherR{at}missouri.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Generation of Pig Induced Pluripotent Stem Cells with a Drug-Inducible System.
Z. Wu, J. Chen, J. Ren, L. Bao, J. Liao, C. Cui, L. Rao, H. Li, Y. Gu, H. Dai, et al. (2009)
J Mol Cell Biol 1, 46-54
   Abstract »    Full Text »    PDF »
Significant Improvement in Cloning Efficiency of an Inbred Miniature Pig by Histone Deacetylase Inhibitor Treatment after Somatic Cell Nuclear Transfer.
J. Zhao, J. W. Ross, Y. Hao, L. D. Spate, E. M. Walters, M. S. Samuel, A. Rieke, C. N. Murphy, and R. S. Prather (2009)
Biol Reprod 81, 525-530
   Abstract »    Full Text »    PDF »
Generation of Induced Pluripotent Stem Cell Lines from Tibetan Miniature Pig.
M. A. Esteban, J. Xu, J. Yang, M. Peng, D. Qin, W. Li, Z. Jiang, J. Chen, K. Deng, M. Zhong, et al. (2009)
J. Biol. Chem. 284, 17634-17640
   Abstract »    Full Text »    PDF »
Production of Piglets after Cryopreservation of Embryos Using a Centrifugation-Based Method for Delipation Without Micromanipulation.
R. Li, C. N. Murphy, L. Spate, D. Wax, C. Isom, A. Rieke, E. M. Walters, M. Samuel, and R. S. Prather (2009)
Biol Reprod 80, 563-571
   Abstract »    Full Text »    PDF »
Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies.
I Kukavica-Ibrulj and R C Levesque (2008)
Lab Anim 42, 389-412
   Abstract »    Full Text »    PDF »
The porcine lung as a potential model for cystic fibrosis.
C. S. Rogers, W. M. Abraham, K. A. Brogden, J. F. Engelhardt, J. T. Fisher, P. B. McCray Jr., G. McLennan, D. K. Meyerholz, E. Namati, L. S. Ostedgaard, et al. (2008)
Am J Physiol Lung Cell Mol Physiol 295, L240-L263
   Abstract »    Full Text »    PDF »
Expression of NANOG, but not POU5F1, points to the stem cell potential of primitive germ cells in neonatal pig testis.
S. Goel, M. Fujihara, N. Minami, M. Yamada, and H. Imai (2008)
Reproduction 135, 785-795
   Abstract »    Full Text »    PDF »
Cytokine Secretion Depends on Gal{alpha}(1,3)Gal Expression in a Pig-to-Human Whole Blood Model.
M. Saethre, M. K. J. Schneider, J. D. Lambris, P. Magotti, G. Haraldsen, J. D. Seebach, and T. E. Mollnes (2008)
J. Immunol. 180, 6346-6353
   Abstract »    Full Text »    PDF »
Generation of Cloned Transgenic Cats Expressing Red Fluorescence Protein.
X. J. Yin, H. S. Lee, X. F. Yu, E. Choi, B. C. Koo, M. S. Kwon, Y. S. Lee, S. J. Cho, G. Z. Jin, L. H. Kim, et al. (2008)
Biol Reprod 78, 425-431
   Abstract »    Full Text »    PDF »
Aggression in cataract-bearing {alpha}-1,3-galactosyltransferase knockout mice.
D. B. Sorensen, K. Dahl, A. K. Ersboll, S. Kirkeby, A. J F d'Apice, and A. K. Hansen (2008)
Lab Anim 42, 34-44
   Abstract »    Full Text »    PDF »
Production and Characterization of Transgenic Mice Systemically Expressing Endo- -Galactosidase C.
S. Watanabe, M. Misawa, T. Matsuzaki, T. Sakurai, T. Muramatsu, T.-a. Yokomine, and M. Sato (2008)
Glycobiology 18, 9-19
   Abstract »    Full Text »    PDF »
Rapidly induced, T-cell independent xenoantibody production is mediated by marginal zone B cells and requires help from NK cells.
S. Li, Y. Yan, Y. Lin, D. M. Bullens, O. Rutgeerts, J. Goebels, C. Segers, L. Boon, A. Kasran, R. De Vos, et al. (2007)
Blood 110, 3926-3935
   Abstract »    Full Text »    PDF »
Ubiquitin C-Terminal Hydrolase-Activity Is Involved in Sperm Acrosomal Function and Anti-Polyspermy Defense During Porcine Fertilization.
Y.-J. Yi, G. Manandhar, M. Sutovsky, R. Li, V. Jonakova, R. Oko, C.-S. Park, R. S Prather, and P. Sutovsky (2007)
Biol Reprod 77, 780-793
   Abstract »    Full Text »    PDF »
Identification, Isolation, and In Vitro Culture of Porcine Gonocytes.
S. Goel, M. Sugimoto, N. Minami, M. Yamada, S. Kume, and H. Imai (2007)
Biol Reprod 77, 127-137
   Abstract »    Full Text »    PDF »
Production of Live Piglets Following Cryopreservation of Embryos Derived from In Vitro-Matured Oocytes.
H. Nagashima, K. Hiruma, H. Saito, R. Tomii, S. Ueno, N. Nakayama, H. Matsunari, and M. Kurome (2007)
Biol Reprod 76, 900-905
   Abstract »    Full Text »    PDF »
Bioelectric Properties of Chloride Channels in Human, Pig, Ferret, and Mouse Airway Epithelia.
X. Liu, M. Luo, L. Zhang, W. Ding, Z. Yan, and J. F. Engelhardt (2007)
Am. J. Respir. Cell Mol. Biol. 36, 313-323
   Abstract »    Full Text »    PDF »
Premature Chromosome Condensation Is Not Essential for Nuclear Reprogramming in Bovine Somatic Cell Nuclear Transfer.
L.-Y. Sung, P.-C. Shen, B.-S. Jeong, J. Xu, C.-C. Chang, W. T.K. Cheng, J.-S. Wu, S.-N. Lee, D. Broek, D. Faber, et al. (2007)
Biol Reprod 76, 232-240
   Abstract »    Full Text »    PDF »
Reduction of hyperacute rejection and protection of metabolism and function in hearts of human decay accelerating factor (hDAF)-expressing pigs.
R. T. Smolenski, M. Forni, M. Maccherini, M. L. Bacci, E. M. Slominska, H. Wang, P. Fornasari, R. Giovannoni, F. Simeone, A. Zannoni, et al. (2007)
Cardiovasc Res 73, 143-152
   Abstract »    Full Text »    PDF »
Porcine Endothelial Cells and Iliac Arteries Transduced with AdenoIL-4 Are Intrinsically Protected, through Akt Activation, against Immediate Injury Caused by Human Complement.
S. M. Black, J. F. Grehan, A. L. Rivard, B. A. Benson, A. E. Wahner, A. E. Koch, B. K. Levay-Young, and A. P. Dalmasso (2006)
J. Immunol. 177, 7355-7363
   Abstract »    Full Text »    PDF »
Full-Term Development of Rat after Transfer of Nuclei from Two-Cell Stage Embryos.
E. Popova, M. Bader, and A. Krivokharchenko (2006)
Biol Reprod 75, 524-530
   Abstract »    Full Text »    PDF »
Proteomic Analysis of the Extraembryonic Tissue from Cloned Porcine Embryos.
J.-I. Chae, S.-K. Cho, J.-W. Seo, T.-S. Yoon, K.-S. Lee, J.-H. Kim, K.-K. Lee, Y.-M. Han, and K. Yu (2006)
Mol. Cell. Proteomics 5, 1559-1566
   Abstract »    Full Text »    PDF »
Cloned Transgenic Swine Via In Vitro Production and Cryopreservation.
R. Li, L. Lai, D. Wax, Y. Hao, C. N. Murphy, A. Rieke, M. Samuel, M. L. Linville, S. W. Korte, R. W. Evans, et al. (2006)
Biol Reprod 75, 226-230
   Abstract »    Full Text »    PDF »
Xenograft rejection--all that glitters is not Gal.
B. Sprangers, M. Waer, and A. D. Billiau (2006)
Nephrol. Dial. Transplant. 21, 1486-1488
   Full Text »    PDF »
Biological and biomaterial approaches for improved islet transplantation..
A. S. Narang and R. I. Mahato (2006)
Pharmacol. Rev. 58, 194-243
   Abstract »    Full Text »    PDF »
Rabbits generated from fibroblasts through nuclear transfer..
S. Li, X. Chen, Z. Fang, J. Shi, and H. Z Sheng (2006)
Reproduction 131, 1085-1090
   Abstract »    Full Text »    PDF »
Functional disruption of the prion protein gene in cloned goats..
G. Yu, J. Chen, H. Yu, S. Liu, J. Chen, X. Xu, H. Sha, X. Zhang, G. Wu, S. Xu, et al. (2006)
J. Gen. Virol. 87, 1019-1027
   Abstract »    Full Text »    PDF »
The Molecular Basis for Gal{alpha}(1,3)Gal Expression in Animals with a Deletion of the {alpha}1,3Galactosyltransferase Gene.
J. Milland, D. Christiansen, B. D. Lazarus, S. G. Taylor, P. X. Xing, and M. S. Sandrin (2006)
J. Immunol. 176, 2448-2454
   Abstract »    Full Text »    PDF »
Xenotransplantation--current status and future perspectives..
E. Cozzi, E. Bosio, M. Seveso, M. Vadori, and E. Ancona (2006)
Br. Med. Bull. 75-76, 99-114
   Abstract »    Full Text »    PDF »
CD80/CD86 Costimulation Regulates Acute Vascular Rejection.
K. A. Hosiawa, H. Wang, M. E. DeVries, B. Garcia, W. Liu, D. Zhou, A. Akram, J. Jiang, H. Sun, M. J. Cameron, et al. (2005)
J. Immunol. 175, 6197-6204
   Abstract »    Full Text »    PDF »
Donor Lymphocyte Infusion Induces Long-Term Donor-Specific Cardiac Xenograft Survival through Activation of Recipient Double-Negative Regulatory T Cells.
W. Chen, D. Zhou, J. R. Torrealba, T. K. Waddell, D. Grant, and L. Zhang (2005)
J. Immunol. 175, 3409-3416
   Abstract »    Full Text »    PDF »
Patient-Specific Embryonic Stem Cells Derived from Human SCNT Blastocysts.
W. S. Hwang, S. I. Roh, B. C. Lee, S. K. Kang, D. K. Kwon, S. Kim, S. J. Kim, S. W. Park, H. S. Kwon, C. K. Lee, et al. (2005)
Science 308, 1777-1783
   Abstract »    Full Text »    PDF »
New Technologies for Organ Replacement and Augmentation.
M. Cascalho and J. L. Platt (2005)
Mayo Clin. Proc. 80, 370-378
   Abstract »    PDF »
A Novel Method for the Production of Transgenic Cloned Pigs: Electroporation-Mediated Gene Transfer to Non-Cultured Cells and Subsequent Selection with Puromycin.
S. Watanabe, M. Iwamoto, S.-i. Suzuki, D. Fuchimoto, D. Honma, T. Nagai, M. Hashimoto, S. Yazaki, M. Sato, and A. Onishi (2005)
Biol Reprod 72, 309-315
   Abstract »    Full Text »    PDF »
Nuclear Remodeling and Reprogramming in Transgenic Pig Production.
R. S. Prather, P. Sutovsky, and J. A. Green (2004)
Experimental Biology and Medicine 229, 1120-1126
   Abstract »    Full Text »    PDF »
Role of Messenger RNA Expression of Platelet Activating Factor and Its Receptor in Porcine In Vitro-Fertilized and Cloned Embryo Development.
S. H. Lee, D. Y. Kim, D. H. Nam, S. H. Hyun, G. S. Lee, H. S. Kim, C.-K. Lee, S. K. Kang, B. C. Lee, and W. S. Hwang (2004)
Biol Reprod 71, 919-925
   Abstract »    Full Text »    PDF »
Cryopreservation of Porcine Embryos Derived from In Vitro-Matured Oocytes.
R. Esaki, H. Ueda, M. Kurome, K. Hirakawa, R. Tomii, H. Yoshioka, H. Ushijima, M. Kuwayama, and H. Nagashima (2004)
Biol Reprod 71, 432-437
   Abstract »    Full Text »    PDF »
Porcine Endogenous Retrovirus Transmission Characteristics of Galactose {alpha}1-3 Galactose-Deficient Pig Cells.
G. Quinn, J. C. Wood, D. J. J. Ryan, K. M. Suling, K. M. Moran, D. L. Kolber-Simonds, J. L. Greenstein, H.-J. Schuurman, R. J. Hawley, and C. Patience (2004)
J. Virol. 78, 5805-5811
   Abstract »    Full Text »    PDF »
Reduced Sensitivity to Human Serum Inactivation of Enveloped Viruses Produced by Pig Cells Transgenic for Human CD55 or Deficient for the Galactosyl-{alpha}(1-3) Galactosyl Epitope.
S. Magre, Y. Takeuchi, G. Langford, A. Richards, C. Patience, and R. Weiss (2004)
J. Virol. 78, 5812-5819
   Abstract »    Full Text »    PDF »
Telomere Lengths in Cloned Transgenic Pigs.
L. Jiang, D. B. Carter, J. Xu, X. Yang, R. S. Prather, and X. C. Tian (2004)
Biol Reprod 70, 1589-1593
   Abstract »    Full Text »    PDF »
The first cell cycle after transfer of somatic cell nuclei in a non-human primate.
S.-C. Ng, N. Chen, W.-Y. Yip, S.-L. Liow, G.-Q. Tong, B. Martelli, L. G. Tan, and P. Martelli (2004)
Development 131, 2475-2484
   Abstract »    Full Text »    PDF »
Lack of Galactose-{alpha}-1,3-Galactose Expression on Porcine Endothelial Cells Prevents Complement-Induced Lysis but Not Direct Xenogeneic NK Cytotoxicity.
B. C. Baumann, P. Forte, R. J. Hawley, R. Rieben, M. K. J. Schneider, and J. D. Seebach (2004)
J. Immunol. 172, 6460-6467
   Abstract »    Full Text »    PDF »
Induction of human T-cell tolerance to porcine xenoantigens through mixed hematopoietic chimerism.
P. Lan, L. Wang, B. Diouf, H. Eguchi, H. Su, R. Bronson, D. H. Sachs, M. Sykes, and Y.-G. Yang (2004)
Blood 103, 3964-3969
   Abstract »    Full Text »    PDF »
Transgenic pigs expressing plant genes.
H. Niemann (2004)
PNAS 101, 7211-7212
   Full Text »    PDF »
Production of {alpha}-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations.
D. Kolber-Simonds, L. Lai, S. R. Watt, M. Denaro, S. Arn, M. L. Augenstein, J. Betthauser, D. B. Carter, J. L. Greenstein, Y. Hao, et al. (2004)
PNAS 101, 7335-7340
   Abstract »    Full Text »    PDF »
Xenotransplantation and the Future of Renal Replacement.
M. Cascalho, B. M. Ogle, and J. L. Platt (2004)
J. Am. Soc. Nephrol. 15, 1106-1112
   Full Text »    PDF »
Limited infection without evidence of replication by porcine endogenous retrovirus in guinea pigs.
T. Argaw, W. Colon-Moran, and C. A. Wilson (2004)
J. Gen. Virol. 85, 15-19
   Abstract »    Full Text »    PDF »
Intracellularly Expressed Single-Domain Antibody against p15 Matrix Protein Prevents the Production of Porcine Retroviruses.
S. Dekker, W. Toussaint, G. Panayotou, T. de Wit, P. Visser, F. Grosveld, and D. Drabek (2003)
J. Virol. 77, 12132-12139
   Abstract »    Full Text »    PDF »
Cross-Reactivity between Swine Leukocyte Antigen and Human Anti-HLA-Specific Antibodies in Sensitized Patients Awaiting Renal Transplantation.
I. D. Varela, P. S. Mozo, A. C. Cortes, C. A. Blanco, and F. V. Canedo (2003)
J. Am. Soc. Nephrol. 14, 2677-2683
   Abstract »    Full Text »    PDF »
Production of Cloned Pigs by Whole-Cell Intracytoplasmic Microinjection.
J.-W. Lee, S.-C. Wu, X. C. Tian, M. Barber, T. Hoagland, J. Riesen, K.-H. Lee, C.-F. Tu, W. T.K. Cheng, and X. Yang (2003)
Biol Reprod 69, 995-1001
   Abstract »    Full Text »    PDF »
Production of Nuclear Transfer-Derived Piglets Using Porcine Fetal Fibroblasts Transfected with the Enhanced Green Fluorescent Protein.
S. Hyun, G. Lee, D. Kim, H. Kim, S. Lee, D. Nam, Y. Jeong, S. Kim, S. Yeom, S. Kang, et al. (2003)
Biol Reprod 69, 1060-1068
   Abstract »    Full Text »    PDF »
Production of {alpha}1,3-Galactosyltransferase-Knockout Cloned Pigs Expressing Human {alpha}1,2-Fucosylosyltransferase.
J. J. Ramsoondar, Z. Machaty, C. Costa, B. L. Williams, W. L. Fodor, and K. R. Bondioli (2003)
Biol Reprod 69, 437-445
   Abstract »    Full Text »    PDF »
Apoptosis and In Vitro Development of Preimplantation Porcine Embryos Derived In Vitro or by Nuclear Transfer.
Y. Hao, L. Lai, J. Mao, G.-S. Im, A. Bonk, and R. S. Prather (2003)
Biol Reprod 69, 501-507
   Abstract »    Full Text »    PDF »
Improvements in Cloning Efficiencies May Be Possible by Increasing Uniformity in Recipient Oocytes and Donor Cells.
K. Miyoshi, S. J. Rzucidlo, S. L. Pratt, and S. L. Stice (2003)
Biol Reprod 68, 1079-1086
   Abstract »    Full Text »    PDF »
Xenotransplantation: where are we today?.
M D Dooldeniya and A N Warrens (2003)
J R Soc Med 96, 111-117
   Full Text »    PDF »
Immunity to the {alpha}(1,3)Galactosyl Epitope Provides Protection in Mice Challenged with Colon Cancer Cells Expressing {alpha}(1,3)Galactosyl-transferase: A Novel Suicide Gene for Cancer Gene Therapy.
R. C. Unfer, D. Hellrung, and C. J. Link Jr. (2003)
Cancer Res. 63, 987-993
   Abstract »    Full Text »    PDF »
Production of alpha 1,3-Galactosyltransferase-Deficient Pigs.
C. J. Phelps, C. Koike, T. D. Vaught, J. Boone, K. D. Wells, S.-H. Chen, S. Ball, S. M. Specht, I. A. Polejaeva, J. A. Monahan, et al. (2003)
Science 299, 411-414
   Abstract »    Full Text »    PDF »
Porcine Endothelial Cells, Unlike Human Endothelial Cells, Can Be Killed by Human CTL Via Fas Ligand and Cannot Be Protected by Bcl-2.
L. Zheng, L.-H. Ben, J. S. Pober, and A. L. M. Bothwell (2002)
J. Immunol. 169, 6850-6855
   Abstract »    Full Text »    PDF »
Spatial and Temporal Inhomogeneities During Ca2+ Release From the Sarcoplasmic Reticulum in Pig Ventricular Myocytes.
F. R. Heinzel, V. Bito, P. G.A. Volders, G. Antoons, K. Mubagwa, and K. R. Sipido (2002)
Circ. Res. 91, 1023-1030
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of Porcine Endogenous Retroviruses Released from Porcine and Infected Human Cells by Heterotrimeric Protein Complex NF-Y and Impact of Immunosuppressive Drugs.
G. Scheef, N. Fischer, E. Flory, I. Schmitt, and R. R. Tonjes (2002)
J. Virol. 76, 12553-12563
   Abstract »    Full Text »    PDF »
Efficient Production of Transgenic Cloned Calves Using Preimplantation Screening.
S.-H. Chen, T. D. Vaught, J. A. Monahan, J. Boone, E. Emslie, P. M. Jobst, A. E. Lamborn, A. Schnieke, L. Robertson, A. Colman, et al. (2002)
Biol Reprod 67, 1488-1492
   Abstract »    Full Text »    PDF »
Characterization of Porcine Endogenous Retrovirus {gamma}pro-pol Nucleotide Sequences.
N. Klymiuk, M. Muller, G. Brem, and B. Aigner (2002)
J. Virol. 76, 11738-11743
   Abstract »    Full Text »    PDF »
Structural Basis of Ordered Binding of Donor and Acceptor Substrates to the Retaining Glycosyltransferase, alpha -1,3-Galactosyltransferase.
E. Boix, Y. Zhang, G. J. Swaminathan, K. Brew, and K. R. Acharya (2002)
J. Biol. Chem. 277, 28310-28318
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)