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Characterization of mice carrying multiple mutant genes which cause the different immunological defects.

携带导致不同免疫缺陷的多种突变基因的小鼠的特征。

基本信息

批准号：
03404068
负责人：
HAYAKAWA Jun-ichiro
金额：
$ 7.23万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03404068/
关键词：
mouse immunodeficient beige xid carcinogenesis UV irradiation bone marrow scid 骨髄細胞免疫不全可移植性 NK細胞

项目摘要

Multiple mutants strains, KSN-bg, KSN-xid, KSN-bg ; xid were bred from a nude strain, KSN.Each strain of mice has good reproduction performance and could be supplied for a small size experiment. Genetic profiles of these strains including microsatellite markers were identical so for examined loci, indicating these strains are congenic each other.. NK-cell activity of mice carrying beige gene, KSN-bg and KSN-bg ; xid was significantly reduced, although florescence-activated cell analysis of spleen cells indicated NK cells labeled with asialo-GM1 antibody were not decreased in mice with beige gene. This indicates that the reduced NK cell activity by beige mutation is due to the functional impairment of NK cells. The cell analysis also indicates that xid mutation induces the decrease in number of B cells in spleen and the amounts of IgG and IgM in serum. However, the comparison of the transplalntability of 7 human tumor cell lines in KSN,KSN-bg and KSN-xid mice, indicated no advantages in … More the double-mutant mice. The transplantability of human tumors in nude/bg/xid mice is now under investigation. These two kinds of double-mutant mice did not provide a model for human dirofilariasis. The SCID mice with beige mutation were also bred from the cross between C.B-17 SCID and KSN-bg mice. The introduction of beige mutation into SCID mice resulted in the significant reduction of NK cell activity and the transplantation of rat bone marrow experiments showed that SCID-bg mice take more easily than SCID mice, which result more severe Graft-versus-host reaction in the SCID-bg mice. In order to examine the surveillance effect of NK-cell activity in carcinogenesis, the tumor induction after UVB-irradiation were compared between KSN and KSN-bg mice at the daily doses of 160 and 320 J/m^2. At 160 J/m^2/day, significantly higher induction of skin tumor in KSN-bg mice than in KSN mice was observed, but at higher dose of 320 J/m^2/day higher induction was fouund in KSN mice. The results suggested that the role of NK-cell activity in UV-carcinogenesis, if any, is very marginal and after only very low dose of UVB-irradiation, Less

从裸小鼠KSN中选育出多突变株KSN-bg、KSN-xid、KSN-bg ; xid，各品系小鼠均具有良好的繁殖性能，可供小型实验使用。这些菌株包括微卫星标记在内的遗传图谱完全相同，表明这些菌株是同源的。携带beige基因、KSN-bg和KSN-bg ; xid的小鼠的NK细胞活性显著降低，尽管脾细胞的荧光激活细胞分析表明，在具有beige基因的小鼠中，无唾液酸-GM 1抗体标记的NK细胞没有减少。这表明米色突变导致的NK细胞活性降低是由于NK细胞的功能受损。细胞分析也表明xid突变导致脾脏中B细胞数量和血清中IgG和IgM含量的减少。然而，7种人肿瘤细胞系在KSN、KSN-bg和KSN-xid小鼠中的可移植性的比较表明， ...更多信息双突变小鼠人肿瘤在裸鼠/bg/xid中的可移植性目前正在研究中。这两种双突变小鼠不能作为人类恶丝虫病的动物模型。还从C.B-17 SCID小鼠和KSN-bg小鼠之间的杂交培育具有米色突变的SCID小鼠。将beige突变导入SCID小鼠后，NK细胞活性明显降低，大鼠骨髓移植实验表明，SCID-bg小鼠比SCID小鼠更易发生移植物抗宿主反应。为了检查NK细胞活性在致癌过程中的监测作用，比较了每日剂量为160和320 J/m^2的KSN和KSN-bg小鼠在UVB照射后的肿瘤诱导情况。在160 J/m^2/天剂量下，观察到KSN-bg小鼠的皮肤肿瘤诱导率显著高于KSN小鼠，但在320 J/m^2/天的较高剂量下，KSN小鼠的诱导率较高。结果表明，NK细胞活性在紫外线致癌作用中的作用，如果有的话，是非常边缘的，只有在非常低剂量的UVB照射后，