Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/lty/Bcg genes on chromosome 1

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Abstract

HUMAN type 1 (insulin-dependent) diabetes is a common autoimmune disease of the insulin-producing β cells of the pancreas which is caused by both genetic and environmental factors1,2. Several features of the genetics and immunopathology of diabetes in nonobese diabetic (NOD) mice are shared with the human disease1,3,4. Of the three diabetes-susceptibility genes, Idd-1 (refs 5–7), -3 and -4 (ref. 4) that have been mapped in mice to date, only in the case of Idd-1 is there any evidence for the identity of the gene product: allelic variation within the murine immune response /-A/3 gene and its human homologue HLA-DQB1 correlates with susceptibility, implying that I–Aβ is a component of Idd-1 (refs 5–11). We report here the mapping of Idd-5 to the proximal region of mouse chromosome 1. This region contains at least two candidate susceptibility genes, the interleukin-1 receptor gene (Il-lrl; ref. 12) and Lsh/Ity/Bcg (refs 13-19), which encodes resistance to bacterial and parasitic infections and affects the function of macrophages.

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