Yu Guohua, Chen Jianquan, Yu Huiqing, Liu Siguo, Chen Juan, Xu Xujun, Sha Hongying, Zhang Xufeng, Wu Guoxiang, Xu Shaofu, Cheng Guoxiang
Shanghai Transgenic Research Center, 88 Cai-Lun Road, Shanghai 201203, China.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai, 200031, China.
J Gen Virol. 2006 Apr;87(Pt 4):1019-1027. doi: 10.1099/vir.0.81384-0.
The cellular prion protein (PrPC), a membrane glycoprotein anchored to the outer surface of neurons, lymphocytes and other cells, is associated directly with the pathogenesis of the transmissible spongiform encephalopathies (TSEs) occurring mainly in humans, cattle, sheep and goats. Although mice lacking PrPC develop and reproduce normally and are resistant to scrapie infection, large animals lacking PrPC, especially those species in which TSE occurs naturally, are currently not available. Here, five live PRNP+/- goats cloned by gene targeting are reported. Detailed RNA-transcription and protein-expression analysis of one PRNP+/- goat showed that one allele of the caprine PRNP gene had been disrupted functionally. No gross abnormal development or behaviour could be seen in these PRNP+/- goats up to at least 3 months of age. These heterozygous PRNP+/- goats are ready to be used in producing homozygous PRNP-/- goats in which no PrPC should be expressed.
细胞朊蛋白（PrPC）是一种锚定在神经元、淋巴细胞和其他细胞外表面的膜糖蛋白，与主要发生在人类、牛、绵羊和山羊身上的传染性海绵状脑病（TSEs）的发病机制直接相关。尽管缺乏PrPC的小鼠发育和繁殖正常且对瘙痒病感染具有抗性，但目前尚无缺乏PrPC的大型动物，尤其是那些自然发生TSE的物种。在此，报道了通过基因靶向克隆的五只存活的PRNP+/-山羊。对一只PRNP+/-山羊进行的详细RNA转录和蛋白质表达分析表明，山羊PRNP基因的一个等位基因已在功能上被破坏。在这些PRNP+/-山羊中，至少在3个月大之前未观察到明显的异常发育或行为。这些杂合的PRNP+/-山羊已准备好用于培育不表达PrPC的纯合PRNP-/-山羊。
