Downregulation of the circadian rhythm related gene Arntl2 suppresses diabetes protection in Idd6 NOD.C3H congenic mice.

1. Our previous studies of the murine genetic locus Idd6 revealed the aryl hydrocarbon receptor nuclear translocator-like protein 2 (Arntl2) as a candidate gene for type 1 diabetes; and in Idd6 NOD.C3H congenic mice, Arntl2 upregulation is linked to decreased diabetes development. 2. In the present study, shRNA plasmids capable of suppressing Arntl2 expression were developed and given to diabetes resistant NOD.C3H congenic mice by hydrodynamic tail vein injection. The effects of Arntl2 suppression on diabetes incidence and immune cell numbers were investigated. 3. Diabetes incidence was increased by Arntl2 mRNA interference in the congenic strain and this was associated with an increase in CD4(+) T cells and a decrease in regulatory T cells in the peripheral immune system. 4. These results provide additional support for the protective role of the Arntl2 gene located in locus Idd6 in diabetes progression in NOD.C3H congenic mice.