The Idd6.2 diabetes susceptibility region controls defective expression of the Lrmp gene in nonobese diabetic (NOD) mice
2007 (English)In: Immunogenetics, ISSN 0093-7711, Vol. 59, no 5, 407-416 p.Article in journal (Refereed) Published
The identification of genes mediating susceptibility to type 1 diabetes (T1D) remains a challenging task. Using a positional cloning approach based on the analysis of nonobese diabetic (NOD) mice congenic over the Idd6 diabetes susceptibility region, we found that the NOD allele at this locus mediates lower mRNA expression levels of the lymphoid restricted membrane protein gene (Lrmp/Jaw1). Analysis of thymic populations indicates that Lrmp is expressed mainly in immature thymocytes. The Lrmp gene encodes a type 1 transmembrane protein that localizes to the ER membrane and has homology to the inositol 1,4,5-triphosphate receptor-associated cGMP kinase substrate gene, which negatively regulates intracellular calcium levels. We hypothesize that the observed decrease in expression of the Lrmp gene in NOD mice may constitute a T1D susceptibility factor in the Idd6 region.
Place, publisher, year, edition, pages
2007. Vol. 59, no 5, 407-416 p.
Animals, Bone Marrow/immunology, Diabetes Mellitus; Type 1/*genetics, Gene Expression, Genetic Predisposition to Disease, Membrane Proteins/*genetics, Mice, Mice; Inbred NOD, RNA; Messenger/metabolism, Spleen/immunology, Thymus Gland/immunology, Up-Regulation
IdentifiersURN: urn:nbn:se:umu:diva-7758DOI: 10.1007/s00251-007-0194-xPubMedID: 17353998OAI: oai:DiVA.org:umu-7758DiVA: diva2:147429