Abstract
Abstract Type 1 diabetes (T1D) is an autoimmune disease resulting from the complex interaction of multiple genetic and environmental factors. The nonobese diabetic (NOD) mouse has proven to be a useful model for investigating T1D susceptibility loci and their immunological effects upon disease progression. We have mapped a NOD diabetes susceptibility locus, termed Idd11, on chromosome 4 (Chr4). A panel of congenic NOD mouse strains, harbouring different C57BL/6 (B6, a diabetes-resistant strain)-derived intervals for Chr4, localized Idd11 to an ~7kb interval. Comparison of diabetes incidence and crossover breakpoints for these strains suggested that a haplotype for this locus underlies T1D susceptibility in NOD mice. Based on publicly available databases, the Idd11 haplotype is located within a predicted gene of unknown function (AK005651). Genomic characterization of AK005651 reveals that this novel gene encodes multiple splice isoforms and open-reading frames, none of which has homology with known proteins. Preliminary expression analysis also indicates that AK005651 is differentially expressed in tissues relevant to T1D, with NOD mice demonstrating altered splicing and reduced expression compared to diabetes-resistant strains. Ongoing studies aim to determine the effect of Idd11 / AK005651 on T1D pathogenesis.
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