CHARACTERIZATION OF 3 DIFFERENT TRANSGENIC MOUSE LINES THAT CARRY HUMAN POLIOVIRUS RECEPTOR GENE - INFLUENCE OF THE TRANSGENE EXPRESSION ON PATHOGENESIS
CHARACTERIZATION OF 3 DIFFERENT TRANSGENIC MOUSE LINES THAT CARRY HUMAN POLIOVIRUS RECEPTOR GENE - INFLUENCE OF THE TRANSGENE EXPRESSION ON PATHOGENESIS
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DOI：
10.1007/bf01310797
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发表时间：
1994-01-01
影响因子：
2.7
通讯作者：
NOMOTO, A
中科院分区：
文献类型：
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作者：
KOIKE, S;TAYA, C;NOMOTO, A
将人脊髓灰质炎病毒受体（PVR）基因导入小鼠ICR株基因组，建立了3株脊髓灰质炎病毒易感小鼠ICR- pvrtg1、ICR- pvrtg5和ICR- pvrtg21。在这些小鼠品系上进行PVR基因的遗传表征，以确定该基因在中枢神经系统（CNS）中的近似拷贝数、插入位点和表达。该转基因基因分别整合在ICR-PVRTg1、ICR-PVRTg5和ICR-PVRTg21小鼠的第4、12和13号染色体上，并稳定地传递给后代小鼠。ICR-PVRTg1似乎具有最丰富的转基因拷贝数，并且在3个小鼠系中显示出最高的PVR mRNA和膜相关PVR蛋白水平。ICR-PVRTg21和ICR-PVRTg5分别处于中等和最低水平。在中枢神经系统中，PVR mRNA仅在脊髓和脑干神经元中检测到高水平，脊髓灰质炎病毒可以复制，这表明PVR mRNA的表达赋予中枢神经系统中脊髓灰质炎病毒的细胞特异性。ICR-PVRTg1和ICR-PVRTg5对脊髓灰质炎病毒的敏感性分别最高和最低，而ICR-PVRTg21介于两者之间。这些结果可能表明小鼠的脊髓灰质炎病毒敏感性归因于PVR的相对表达水平。
Three transgenic mouse lines, ICR-PVRTg1, ICR-PVRTg5, and ICR-PVRTg21, which are susceptible to poliovirus, have been established by introducing the human gene for poliovirus receptor (PVR) into the genome of mouse strain ICR. Genetic characterizations of the PVR gene were carried out on these mouse lines to define the approximate copy number, insertion site, and expression of the transgene in the central nervous system (CNS). The transgene was integrated in the chromosome 4, 12, and 13 of ICR-PVRTg1, ICR-PVRTg5 and ICR-PVRTg21 mice, respectively, and was stably transmitted to progeny mice. ICR-PVRTg1 appeared to have the most abundant copy numbers of the transgene and showed the highest level of PVR mRNA and membrane associated PVR protein in the CNS among the three mouse lines. Those in ICR-PVRTg21 and ICR-PVRTg5 were at intermediate and lowest levels, respectively. In the CNS, PVR mRNA was detected at high levels only in neurons of the spinal cord and brain stem where poliovirus can replicate, suggesting that the PVR mRNA expression confers cell specificity to poliovirus in the CNS. ICR-PVRTg1 and ICR-PVRTg5 showed the highest and the lowest sensitivity to poliovirus, respectively, whereas ICR-PVRTg21 was in-between. These results may suggest that poliovirus sensitivity of the mice is attributed to relative levels of PVR expression.