Joint study of antigen presenting activity in NOD mice

NOD小鼠已被用作研究多基因疾病的IDDM模型，因为至少有16个不同的基因座被报道，称为IDD。然而，除了与MHC II类相关的Idd1外，它们的实质性基因还不清楚。在本学年，我们在IDDS或其他疾病中探索了NOD小鼠免疫应答的相关基因，包括抗原提呈活性，并获得了以下结果。1)将MSM株的染色体片段导入NOD小鼠的遗传背景中，发现NOD-Idd4小鼠存在明显的胰岛素炎症，而NOD-Idd3小鼠则不明显，并且在D3MIT169和D3MIT181之间存在一个含有IL-2基因的Idd3区域，与严重的Idd 3和Id3相关。事实上，在体外，通过CD3交联，MSM的T细胞产生IL-2的水平高于NOD。3)由于逆转录病毒可能整合到基因组中，导致某些基因的突变，我们检测了C型逆转录病毒env基因片段的特定插入，发现在NOD小鼠18号染色体上有一个env插入，该插入定位在负责抗原递呈的II基因的1 cM以内。然而，我们还没有得到Env插入有助于II基因结构或功能改变的直接证据。从这些数据推测，我们在NOD小鼠中获得的II基因的低表达可能来自于IL-2的低产生，其基因位于Idd3。还需要进一步的分析。

The NOD mice have been used as a IDDM model for studying multigenic diseases because at least 16 different loci, named Idd, have been reported. However, their substantial genes are remained unclear except Idd1 which is linked to MHC class II.In this academic year, we explored the related genes for immune responsiveness including antigen presenting activity of NOD mice among Idds or others, and obtained the followings. 1) In use of two congenic staine for Idd 3 and Idd4 by introducing chromosomal segments from MSM stain into the genetic background of NOD mice, we found that insulitis is clear in NOD-Idd4 but not in NOD-Idd3, and that a region responsible for severe insulitis is located in the Idd3 region between D3MIT169 and D3MIT181 including IL-2 gene. In fact, the level of IL-2 production from T cells of MSM was higher than that of NOD by crosslinking CD3 in vitro. thus, it is strongly suggested that IL-2 is a plausible candidate gene of Idd3.2) Since retrovirus may be integrated into genom to induce mutation of certain genes, we examined particular insertions of Env gene fragment of C-Type retrovirus and found a Env insertion into 18 chromosome of NOD mice in which the insertion was mapped within 1cM of Ii gene responsible to antigen presentation. However, we have not obtained a direct evidence that Env insertion contributes for alteration of Ii gene structure or its function. In putative conclusion from these data, the lower Ii gene expression which we obtained in NOD mice may come from the low production of IL-2 whose gene is located in Idd3. Further analysis is required.