Production of alpha 1,3-galactosyltransferase-deficient pigs.-猫眼课题宝

DOI：

发表时间：

2003

期刊：

Science

影响因子：

56.9

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

C. Phelps;C. Koike;T. Vaught;J. Boone;K. Wells;Shu-Hung Chen;S. Ball;S. Specht;I. Polejaeva;Jeff A. Monahan;P. Jobst;Sugandha B. Sharma;Ashley E. Lamborn;A. S. Garst;M. Moore;A. Demetris;W. Rudert;R. Bottino;S. Bertera;M. Trucco;T. Starzl;Yifan Dai;D. Ayares

酶α 1，3-半乳糖基转移酶（α 1，3GT或GGTA 1）合成α 1，3-半乳糖（α 1，3Gal）表位（Galalpha 1，3Galbeta 1，4GlcNAc-R），其是引起猪-人异种移植超急性排斥反应的主要异种抗原。从猪器官中完全去除α 1，3Gal是异种移植成功的关键一步。我们早先报道了在克隆猪中α 1，3GT基因的一个等位基因的靶向破坏。使用基于细菌毒素的选择程序来选择其中基因的第二等位基因被敲除的细胞。测序分析表明，α 1，3GT基因第二等位基因的敲除是由于第9外显子第二个碱基的T → G单点突变导致α 1，3GT蛋白失活。通过连续三轮克隆产生4头健康的α 1，3GT双敲除雌性仔猪。在α 1，3GT基因中携带点突变的仔猪具有重要价值，因为它们将允许生产不含耐药性基因的α 1，3Gal缺陷猪，从而有可能生产更安全的产品供人类使用。

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.

Production of alpha 1,3-galactosyltransferase-deficient pigs.

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