Deletion of the α(1,3)galactosyl transferase (GGTA1) gene and the prion protein (PrP) gene in sheep
Deletion of the α(1,3)galactosyl transferase (GGTA1) gene and the prion protein (PrP) gene in sheep
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DOI：
10.1038/89313
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发表时间：
2001-06-01
影响因子：
46.9
通讯作者：
Clark, AJ
中科院分区：
文献类型：
--
作者：
Denning, C;Burl, S;Clark, AJ
核移植提供了一种基于细胞的途径，用于在一系列动物物种中产生精确的遗传修饰。使用绵羊，我们报告了在胎儿成纤维细胞中两个独立位点的可重复靶向基因缺失。从α（1，3）半乳糖基转移酶（GGTA 1）基因和朊病毒蛋白（PrP）基因中删除了重要区域，α（1，3）半乳糖基转移酶（GGTA 1）基因可能导致异种移植器官的超急性排斥反应，朊病毒蛋白（PrP）基因与人类和动物的海绵状脑病直接相关。使用靶向或非靶向供体细胞的培养物制备重构胚胎。8次妊娠维持至足月，4只PrP-/+羔羊出生。虽然其中三个在出生后不久就死亡了，但一个存活了12天。这些数据表明，可以通过核转移产生携带靶向基因缺失的羔羊。
Nuclear transfer offers a cell-based route for producing precise genetic modifications in a range of animal species. Using sheep, we report reproducible targeted gene deletion at two independent loci in fetal fibroblasts. Vital regions were deleted from the alpha (1,3)galactosyl transferase (GGTA1)gene, which may account for the hyperacute rejection of xenografted organs, and from the prion protein (PrP) gene, which is directly associated with spongiform encephalopathies in humans and animals. Reconstructed embryos were prepared using cultures of targeted or nontargeted donor cells. Eight pregnancies were maintained to term and four PrP-/+ lambs were born. Although three of these perished soon after birth, one survived for 12 days. These data show that lambs carrying targeted gene deletions can be generated by nuclear transfer.