Phelps, CJ and Koike, C and Vaught, TD and Boone, J and Wells, KD and Chen, SH and Ball, S and Specht, SM and Polejaeva, IA and Monahan, JA and Jobst, PM and Sharma, SB and Lamborn, AE and Garst, AS and Moore, M and Demetris, AJ and Rudert, WA and Bottino, R and Bertera, S and Trucco, M and Starzl, TE and Dai, Y and Ayares, DL
(2003)
Production of α1,3-galactosyltransferase-deficient pigs.
Science, 299 (5605).
411 - 414.
ISSN 0036-8075
Abstract
The enzyme α1,3-galactosyltransferase (α1,3GT or GGTA1) synthesizes α1,3galactose (α1,3Gal) epitopes (Galα1,3Galβ1,4GlcNAc-R), which are the major xenoantigens causing hyperacute rejection in pig-to-human xenotransplantation. Complete removal of α1,3Gal from pig organs is the critical step toward the success of xenotransplantation. We reported earlier the targeted disruption of one allele of the α1,3GT gene in cloned pigs. A selection procedure based on a bacteria[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 α1,3GT gene was caused by a T-to-G single point mutation at the second base of exon 9, which resulted in inactivation of the α1,3GT protein. Four healthy α1,3GT double-knockout female piglets were produced by three consecutive rounds of cloning. The piglets carrying a point mutation in the α1,3GT gene hold significant value, as they would allow production of α1,3Gal-deficient pigs free of antibiotic-resistance genes and thus have the potential to make a safer product for human use.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID ![](/images/orcid_id_24x24.png) |
---|
Phelps, CJ | | | | Koike, C | | | | Vaught, TD | | | | Boone, J | | | | Wells, KD | | | | Chen, SH | | | | Ball, S | | | | Specht, SM | | | | Polejaeva, IA | | | | Monahan, JA | | | | Jobst, PM | | | | Sharma, SB | | | | Lamborn, AE | | | | Garst, AS | | | | Moore, M | | | | Demetris, AJ | | | | Rudert, WA | | | | Bottino, R | | | | Bertera, S | | | | Trucco, M | mnt@pitt.edu | MNT | | Starzl, TE | tes11@pitt.edu | TES11 | | Dai, Y | | | | Ayares, DL | | | |
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Centers: |
Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute |
Date: |
17 January 2003 |
Date Type: |
Publication |
Journal or Publication Title: |
Science |
Volume: |
299 |
Number: |
5605 |
Page Range: |
411 - 414 |
DOI or Unique Handle: |
10.1126/science.1078942 |
Institution: |
University of Pittsburgh |
Refereed: |
Yes |
ISSN: |
0036-8075 |
Other ID: |
uls-drl:31735062120906, Starzl CV No. 2182 |
Date Deposited: |
08 Apr 2010 17:37 |
Last Modified: |
04 Feb 2019 15:58 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/5568 |
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