TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis
TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis
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DOI：
10.1073/pnas.1421587112
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发表时间：
2015-03-31
影响因子：
11.1
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
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作者：
Wu, Haibo;Wang, Yongsheng;Zhang, Yong
转录激活子样效应子核酸酶(TALEN)介导的基因组修饰已被成功地应用于各种物种的转基因动物，如小鼠、猪甚至猴子。然而，使用TALEN还没有创造出具有基因敲击功能的转基因牛。在这里，我们报道了转录激活因子样效应子(TALE)镍酶介导的SP110核体蛋白基因(SP110)通过同源重组而被定点敲打，从而培育出抗结核病的牛。体内外攻击和传播实验证明，转基因牛能够控制牛分枝杆菌的生长和繁殖，开启感染后细胞死亡而不是坏死的凋亡途径，并有效抵抗自然界中来自结核牛的低剂量牛分枝杆菌传播。在这项研究中，我们开发了故事昵称来修改荷斯坦-弗里西亚牛的基因组，从而设计出一种可遗传的基因组修改，从而促进对结核病的抗性。
Transcription activator-like effector nuclease (TALEN)-mediated genome modification has been applied successfully to create transgenic animals in various species, such as mouse, pig, and even monkey. However, transgenic cattle with gene knockin have yet to be created using TALENs. Here, we report site-specific knockin of the transcription activator-like effector (TALE) nickase-mediated SP110 nuclear body protein gene (SP110) via homologous recombination to produce tuberculosis-resistant cattle. In vitro and in vivo challenge and transmission experiments proved that the transgenic cattle are able to control the growth and multiplication of Mycobacterium bovis, turn on the apoptotic pathway of cell death instead of necrosis after infection, and efficiently resist the low dose of M. bovis transmitted from tuberculous cattle in nature. In this study, we developed TALE nickases to modify the genome of Holstein-Friesian cattle, thereby engineering a heritable genome modification that facilitates resistance to tuberculosis.