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

KSN-BG、KSN-XID、KSN-BG、XID等多个突变品系是从一株裸鼠KSN中选育而来的，每个品系都有较好的繁殖性能，可供小型实验使用。包括微卫星标记在内的这些菌株的遗传图谱与所检测的基因座相同，表明这些菌株是同源的。携带米色基因、KSN-BG和KSN-BG；XID基因的小鼠的NK细胞活性显著降低，而脾细胞的荧光激活细胞分析显示，携带米色基因的小鼠的NK细胞没有减少。这表明，褐变导致的NK细胞活性降低是由于NK细胞功能受损所致。细胞分析还表明，XID突变可导致小鼠脾B细胞数量减少，血清中Ig G、Ig M含量降低。然而，7种人肿瘤细胞系在Ksn、ksn-BG和ksn-xid小鼠体内的移植能力比较表明，在…中没有优势更多的是双突变小鼠。人肿瘤在裸/BG/XID小鼠体内的可移植性正在研究中。这两种双突变小鼠没有为人类白丝虫病提供模型。米色突变的SCID小鼠也是由C.B-17 SCID小鼠与KSN-BG小鼠杂交而成。在SCID小鼠中引入米色突变导致NK细胞活性显著降低，大鼠骨髓移植实验表明，SCID-BG小鼠比SCID-BG小鼠更容易发生移植物抗宿主反应，从而导致更严重的移植物抗宿主反应。为探讨NK细胞活性在肿瘤发生中的监测作用，比较了KSN和KSN-BG小鼠在日剂量为160和320J/m~2的UVB照射后的肿瘤诱导率。在160J/m~(-2)/d剂量下，KSN-BG小鼠的皮肤肿瘤诱发率显著高于KSN小鼠，但在高剂量(320J/m~(-2)/d)时，KSN小鼠的皮肤肿瘤诱导率明显高于KSN小鼠。结果表明，NK细胞活性在紫外线致癌中的作用，如果有的话，是非常微乎其微的，并且仅在极低剂量的UVB照射后，作用更小。

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