TERADA Eiji Kitasato University, School of Science, Associate Professor, 理学部, 助教授 (10113440)
YONEKAWA Hiromichi Tokyo Metropolitan Institute of Medical Science, Laboratoty Animal Science, Depa, 実験動物研究部門, 室長 (30142110)
|Budget Amount *help
¥6,900,000 (Direct Cost : ¥6,900,000)
Fiscal Year 1997 : ¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1996 : ¥4,500,000 (Direct Cost : ¥4,500,000)
Poliovirus infects only primates, and causes a paralytic poliomyelitis in them. Because of this species specificity, monkeys have been used as an animal model for the study of poliovirus pathogenicity and for safety testing of oral live vaccine strains. To produce a new animal model for poliomyelitis, we produced the transgenic (Tg) mice susceptible to poliovirus by introducing the human poliovirus receptor (PVR) gene into the mouse genome. This Tg mouse model has been proved to become an additional animal model for poliomyelitis.
PVR expression pattern in various tissues of the Tg mouse body, however, was different from that of human body. For example, PVR expressions in the small intestine and the liver, which are easily detected in humans, were hardly observed in the Tg mice. In fact, the Tg mice did not show a significant sensitivity to orally-inoculated poliovirus. To produce a transgenic mouse model whose alimentary tract is highly sensitive to poliovirus, we took advantage of the
upstream segment (12kbp) of the MPH (mouse PVR homolog) gene to regulate expression of the PVR gene, and used a chimera gene, which consisted of the upstream segment of the MPH gene and the structural segment of the PVR gene, as a transgene to produce new Tg mice (MTg mice).
PVR expression pattern in MTg mice is much closer to that in humans as compared with that in the previous Tg mice, that is, PVR expression was easily detected in the small intestine and the liver of MTg mice. However, MTg mice did not show an enhanced sensitivity to orally-inoculated poliovirus.
When we inoculated poliovirus into the liver of the MTg mice, poliovirus replication in the tissue was evident. This phenomena was not observed in the Tg mice previously produced. Thus, the MTg mouse model is unique in regard with susceptibility of the liver to poliovirus, although we failed to produce the Tg mice susceptible to orally-inoculated poliovirus. This unique mouse model may be useful tools to study mechanisms for tissue tropism of poliovirus. Less