|Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥2,400,000 (Direct Cost: ¥2,400,000)
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.