High impact information on Idd10

• While only partial protection from disease is provided by resistance alleles at single non-MHC Idd loci, epistatic interaction between two of the loci, Idd3 and Idd10, produced nearly complete protection from diabetes [1].
• Resistance alleles at two non-major histocompatibility complex-linked insulin-dependent diabetes loci on chromosome 3, Idd3 and Idd10, protect nonobese diabetic mice from diabetes [2].
• cDNA microarrays with >11,000 cDNA clones from an NOD spleen cDNA library were used to identify temporal gene expression changes in NOD mice (1-10 weeks), which spontaneously develop type 1 diabetes, and changes between NOD and NOD congenic mice (NOD.Idd3/Idd10 and NOD.B10Sn-H2(b)), which have near zero incidence of insulitis and diabetes [3].
• Identification of a structurally distinct CD101 molecule encoded in the 950-kb Idd10 region of NOD mice [4].
• In the present study, we used a combination of BAC clone contig construction, polymorphism analysis of DNA from congenic strains, and sequence mining of the human orthologous region to generate an integrated map of the Idd10 region on mouse chromosome 3 [4].

Biological context of Idd10

• Localization of two insulin-dependent diabetes (Idd) genes to the Idd10 region on mouse chromosome 3 [5].
• We found seven genes and one pseudogene in the 950-kb Idd10 region [4].
• Among polygenes conferring susceptibility to type 1 diabetes in the NOD mouse, Idd10 on distal chromosome 3 has been shown to be important for disease susceptibility [6].
• Among seven NOD-related strains studied, the IIS mouse was found to possess a recombinant Idd10 interval with the same sequence at Fcgr1 as the NOD mouse, but a different sequence at Cd101 from that in the NOD mouse with 10 amino acid substitutions [6].
• Bone marrow derived macrophages (BMM) were grown from NOD, C57BL/6J, non-obese non-diabetic (NON) mice, and NOD-related congenic variants differing in the Idd-3, Idd-10/18, or major histocompatibility complex (MHC) region [7].

Other interactions of Idd10

• We have mapped the Idd10 and Idd18 loci to 1.3- and 2.0-cM intervals, respectively, by holding the Idd3 allele constant [8].
• Mapping by genetic interaction: high-resolution congenic mapping of the type 1 diabetes loci Idd10 and Idd18 in the NOD mouse [8].
• Previously, three insulin-dependent diabetes (Idd) genes, Idd3, Idd10, and Idd17, were localized to mouse Chromosome (Chr) 3 [5].
• Diabetogenic NOD-derived alleles at Idd2 (Chr 9), Idd3 (Chr 3), and Idd10 (Chr 3) were segregating in the BC1 [9].
• The frequency of type 1 diabetes in NOD mice congenic for IIS Idd10 (NOD.IISIdd10) was significantly reduced as compared to that in the NOD mouse, despite the presence of the identical Fcgr1 sequence [6].

References