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）的抗性机制，以通过胚胎技术产生MHV抗性小鼠菌株。 SJL和BALB/C小鼠分别具有抗MHV的抗性和易感性。我们推测，从以下发现中在这些小鼠中表达的MHV受体产生的敏感性差异。 1）MHV电阻受到7号染色体上的单个常染色体基因的控制，该染色体也映射了MHV受体基因。 2）易感性在抗性中占主导地位的事实符合以下概念：主要基因产物是使小鼠易感的宿主因素； MHV受体是候选者之一。我们发现，在BALB/C中表达的受体MHVR1比在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敏感性的原因。我们还发现，通过使用F2和BALB/c X SJL之间的后代，在7染色体上，MHV抗性基因和MHV受体基因在7.94 cm的距离内紧密相连。这表明MHV抗性基因可能与MHV抗性基因相似。为了检查这种可能性，正在进行实验，以替代基因替代MHVR1和MHVR2基因。 MHVR2被MHVR1以及MHVR1替换为MHVR1的SJL的敏感性将得出结论我们的假设是否正确。为了制造MHV抗性小鼠，目前正在进行实验，以通过基因靶向敲除MHV受体基因。