权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Production of MHV-resistance mouse by embryo technology

利用胚胎技术生产抗MHV小鼠

基本信息

批准号：
08558089
负责人：
TAGUCHI Fumihiro
金额：
$ 8.77万
依托单位：
Institute of Neuroscience, NCNP
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08558089/
关键词：
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 t

项目摘要

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.

我们研究了小鼠对小鼠肝炎病毒（MHV）的抵抗机制，旨在通过胚胎技术培育出抗MHV小鼠品系。 SJL 和 BALB/c 小鼠分别对 MHV 具有抵抗力和敏感性。根据以下发现，我们推测易感性差异是由这些小鼠中表达的 MHV 受体引起的。 1) MHV 抗性由 7 号染色体上的单个常染色体基因控制，MHV 受体基因也位于该基因上。 2) 易感性优于抗性这一事实符合显性基因产物是使小鼠易感的宿主因素的概念； MHV受体是候选者之一。我们发现 BALB/c 中表达的受体 MHVR1 与 MHV 结合的效率比 SJL 中表达的 MHVR2 高 10 至 100 倍。这种差异可能是这些小鼠之间不同易感性的原因。我们还通过使用F2和BALB/c x SJL回交后代发现MHV抗性基因和MHV受体基因紧密连锁，在7号染色体上距离0.94 cM。这表明MHV抗性基因与MHV受体基因相同的可能性。为了检验这种可能性，正在进行通过基因替换来替换 MHVR1 和 MHVR2 基因的实验。 MHVR2被MHVR1取代的SJL以及MHVR1被MHVR2取代的BALB/c的敏感性将决定我们的假设是否正确。为了制造抗 MHV 小鼠，目前正在进行通过基因打靶敲除 MHV 受体基因的实验。