Disease relevance of Idd5

• Insulin-dependent diabetes loci Idd5 and Idd9 increase sensitivity to experimental autoimmune encephalomyelitis [1].
• In this study, we determined the efficiency with which macrophages from diabetes-prone NOD and diabetes-resistant NOR, Idd5, Balb/c, and C57BL/6 mice phagocytose apoptotic thymocytes and NIT-1 insulinoma cells [2].
• In the present study, we bred the Idd3 and Idd5 chromosomal intervals from NOD mice into non-autoimmune C57BL/6 mice to determine if these intervals recreate a Sjögren's syndrome (SS)-like phenotype [3].
• More than 19 chromosomal intervals (referred to as Idd regions) that contribute to diabetes susceptibility in the NOD mouse model have been identified, but only 2 chromosomal intervals (associated with Idd3 and Idd5) have been shown to control sialadenitis [3].

High impact information on Idd5

• This places it in a region of chromosome 2q that shows conserved synteny with the region of mouse chromosome 1 containing the murine type 1 diabetes gene, Idd5 [4].
• We report that NOD-derived alleles at both the Idd5 and Idd13 loci regulate a T lymphocyte-dependent progression from a benign to a destructive stage of insulitis [5].
• Apoptosis resistance of nonobese diabetic peripheral lymphocytes linked to the Idd5 diabetes susceptibility region [6].
• Congenic strains on both the NOD and NOR backgrounds confirmed the roles of Idd4 and Idd9 in CY-T1D susceptibility and revealed the contribution of a third locus, Idd5 [7].
• Additional expression studies in this work support the hypothesis that this SNP in exon 2 is the genetic variation causing the biological effects of Idd5 [8].

Biological context of Idd5

• On its own, the Idd5 locus provides a significant amount of protection from diabetes (50% reduction from parental frequency) and when combined with another resistance locus (Idd3 on chromosome 3), provides nearly complete protection from diabetes and insulitis [9].
• To determine if the B10 alleles in loci Idd5 and Idd9 could influence susceptibility to autoimmunity in other organs, we compared MOG35-55-induced EAE in NOD mice to that of diabetes-resistant NOD.B10.Idd5 and NOD.B10.Idd9 mice [1].
• For Idd3 and Idd5 we would also not reject a model of additivity on the penetrance scale, which might indicate a disease model mediated by more than one pathway leading to beta-cell destruction and development of diabetes [10].
• 3. The homologues of these genes may reside on human chromosomes 1 or 4 (Idd-3), 17 (Idd-4) and 2q (Idd-5) [11].

Anatomical context of Idd5

• Ctla4, being localized in this chromosomal region and mediating crucial functions in T cell biology, is a logical candidate gene in the Idd5 susceptibility region [12].
• Peritoneal macrophages from NOR and Idd5 NOD congenic mice were more proficient at engulfment than their NOD counterparts [2].
• Since the diabetes-predisposing Idd-5 gene of NOD mice maps close to the IL-1 receptor, we tested NOD bone marrow cells for a defect in synergy between IL-1 and IL-3; no defect was found [13].

Analytical, diagnostic and therapeutic context of Idd5

• Islet allograft tolerance could not be induced in diabetes-resistant NOD.B10 Idd5 and NOD.B10 Idd9 mice [14].

References