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Production of α1,3-galactosyltransferase-deficient pigs

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

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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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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
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
Starzl, TEtes11@pitt.eduTES11
Dai, Y
Ayares, DL
Centers: Other Centers, Institutes, 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: 13 Oct 2017 23:00
URI: http://d-scholarship.pitt.edu/id/eprint/5568

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