CHARACTERIZATION OF 3 DIFFERENT TRANSGENIC MOUSE LINES THAT CARRY HUMAN POLIOVIRUS RECEPTOR GENE - INFLUENCE OF THE TRANSGENE EXPRESSION ONPATHOGENESIS

Three transgenic mouse lines, ICR-PVRTg1, ICR-PVRTg5, and ICR-PVRTg21, which are susceptible to poliovirus, have been established by introdu cing the human gene for poliovirus receptor (PVR) into the genome of m ouse strain ICR. Genetic characterizations of the PVR gene were carrie d out on these mouse lines to define the approximate copy number, inse rtion site, and expression of the transgene in the central nervous sys tem (CNS). The transgene was integrated in the chromosome 4, 12, and 1 3 of ICR-PVRTg1, ICR-PVRTg5 and ICR-PVRTg21 mice, respectively, and wa s stably transmitted to progeny mice. ICR-PVRTg1 appeared to have the most abundant copy numbers of the transgene and showed the highest lev el of PVR mRNA and membrane associated PVR protein in the CNS among th e three mouse lines. Those in ICR-PVRTg21 and ICR-PVRTg5 were at inter mediate and lowest levels, respectively. In the CNS, PVR mRNA was dete cted at high levels only in neurons of the spinal cord and brain stem where poliovirus can replicate, suggesting that the PVR mRNA expressio n confers cell specificity to poliovirus in the CNS. ICR-PVRTg1 and IC R-PVRTg5 showed the highest and the lowest sensitivity to poliovirus, respectively, whereas ICR-PVRTg21 was in-between. These results may su ggest that poliovirus sensitivity of the mice is attributed to relativ e levels of PVR expression.