Production of alpha 1,3-galactosyltransferase-deficient pigs |
| |
| Authors: | Phelps Carol J Koike Chihiro Vaught Todd D Boone Jeremy Wells Kevin D Chen Shu-Hung Ball Suyapa Specht Susan M Polejaeva Irina A Monahan Jeff A Jobst Pete M Sharma Sugandha B Lamborn Ashley E Garst Amy S Moore Marilyn Demetris Anthony J Rudert William A Bottino Rita Bertera Suzanne Trucco Massimo Starzl Thomas E Dai Yifan Ayares David L |
| |
| Institution: | PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA. |
| |
| Abstract: | The enzyme alpha1,3-galactosyltransferase (alpha1,3GT or GGTA1) synthesizes alpha1,3-galactose (alpha1,3Gal) epitopes (Galalpha1,3Galbeta1,4GlcNAc-R), which are the major xenoantigens causing hyperacute rejection in pig-to-human xenotransplantation. Complete removal of alpha1,3Gal from pig organs is the critical step toward the success of xenotransplantation. We reported earlier the targeted disruption of one allele of the alpha1,3GT gene in cloned pigs. A selection procedure based on a bacterial toxin was used to select for cells in which the second allele of the gene was knocked out. Sequencing analysis demonstrated that knockout of the second allele of the alpha1,3GT gene was caused by a T-to-G single point mutation at the second base of exon 9, which resulted in inactivation of the alpha1,3GT protein. Four healthy alpha1,3GT double-knockout female piglets were produced by three consecutive rounds of cloning. The piglets carrying a point mutation in the alpha1,3GT gene hold significant value, as they would allow production of alpha1,3Gal-deficient pigs free of antibiotic-resistance genes and thus have the potential to make a safer product for human use. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
