| Project/Area Number |
08558089
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Laboratory animal science
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| Research Institution | Institute of Neuroscience, NCNP |
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Principal Investigator |
TAGUCHI Fumihiro National Institute of Neuroscience, Division of Animal Models for Human Diseases, Section chief, 室長 (30107429)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Toshio Central Institute for Experimantal Animals, ICLAS Monitorign Center, Section chi, 室長 (20106644)
YAMADA Yasuko National Institute of Infectious Diseases, Animal Center, Chief Researcher, 主任研究員 (20158223)
YAGAMI Kenichi University of Tsukuba, Laboratory Animal Research Center, Professor, 医学部, 教授 (40166476)
佐伯 圭一 国立精神, 神経センター・神経研究所・モデル動物開発部, 流動研究員
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 1998: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1997: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1996: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Mouse hepatitis virus / MHV receptor / MHV resistance / Knockout mouse / gene targeting / mouse hepatitis virus(MHV) / MHY susceptibility / MHY receptor(MHVR) / gene replacement / gene targeting / mouse hepatitis virus / spike protein / viral receptor / transgenic mo:use / gene targetting / receptor-binding site / virus-binding site / transgenic mouse |
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| Research Abstract |
We have studied the resistance mechanisms of mice to mouse hepatitis virus (MHV) in order to produce MHV-resistance mouse strain by embryo technology. SJL and BALB/c mice are resistant and susceptible to MHV, respectively. We speculated that the difference in susceptibility resulted from MHV receptor expressed in these mice from the following findings. 1) MHV resistance is controlled by a single autosomal gene on chromosome 7 on which MHV-receptor gene is also mapped. 2) The fact that susceptibility is dominant over the resistance fits the concept that a dominant gene product is a host factor to make mice susceptible ; MHV receptor is one of the candidates. We found that the receptor MHVR1 expressed in BALB/c was 10 to 100 fold more efficient for MHV binding than the MHVR2 expressed in SJL.This difference could be responsible for the different susceptibility between these mice. We have also found that MHV-resistance gene and MHV-receptor gene were tightly linked, within 0.94 cM distance on chromosome 7, by using F2 and backcrossed progenies between BALB/c x SJL.This suggests the possibility that MHV-resistance gene is identical to MHV-receptor gene. To examine such possibility, experiments are under progress to replace MHVR1 and MHVR2 genes by gene replacement. The susceptibility of SJL whose MHVR2 is replaced by MHVR1 as well as BALB/c whose MHVR1 is replaced by MHVR2 will conclude whether our hypothesis is right or not. To make MHV-resistance mice, experiment is currently in progress to knockout the MHV-receptor genes by gene targeting.
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