| First Author | Serreze DV | Year | 1998 |
| Journal | J Immunol | Volume | 160 |
| Issue | 3 | Pages | 1472-8 |
| PubMed ID | 9570569 | Mgi Jnum | J:44130 |
| Mgi Id | MGI:1195420 | Doi | 10.4049/jimmunol.160.3.1472 |
| Citation | Serreze DV, et al. (1998) Subcongenic analysis of the Idd13 locus in NOD/Lt mice: evidence for several susceptibility genes including a possible diabetogenic role for beta 2-microglobulin. J Immunol 160(3):1472-8 |
| abstractText | Although they share similar to 88% of their genome with NOD mice including the H2(g7) haplotype, NOR mice remain free of T cell-mediated autoimmune diabetes (IDDM), due to non-MHC genes of C57BLKS/J (BKS) origin, NOR IDDM resistance was previously found to be largely controlled by the Idd13 locus within an similar to 24 chi segment on Chromosome 2 encompassing BKS-derived alleles for H3a, B2m, III? and Pcna. NOD stocks carrying subcongenic intervals of NOR Chromosome 2 were utilized to more finely map and determine possible functions of Idd13. NOR-derived H3a-II1 (similar to 6.0 cM) and II1-Pcna (similar to 1.2 cM) intervals both contribute components of IDDM resistance, Hence, the Idd13 locus is more complex than originally thought, since it consists of at least two genes, B2m variants within the H3a-II1 interval may represent one of these, Monoclonal Ab binding demonstrated that dimerizing with the beta(2)m(2) (NOD type) vs beta(2)m(b) isoform (NOR type alters the structural conformation, but not total expression levels of H2(g7) class I molecules (e.g. K-d, D-b), beta(2)m-induced alterations in H2(g7) class I conformation may partially explain findings from bone marrow chimera analyses that ldd13 modulates IDDM development at the level of non- hematopoietically derived cell types controlling selection of diabetogenic T cells and/or pancreatic beta cells targeted by these effectors. Since trans-interactions between relatively common and functionally normal allelic variants mag contribute to IDDM in NOD mice, the search for Idd genes in humans should not be limited to functionally defective variants. |
