A C57BL/10Sn (B10)-derived diabetes resistance Idd9.3 congenic region has been shown to enhance accumulation of CD137<sup>+</sup> regulatory T cells and serum soluble CD137 in NOD mice.
In the current report we reduce the size of the Idd9.3 interval to 1.2Mb containing 15 genes, including one encoding the immune signaling molecule, 4-1BB, which shows amino acid variation between diabetes sensitive and resistant strains.
Paradoxically, transgenic non-obese diabetic (NOD) mice overexpressing membrane-bound agonistic single-chain anti-4-1BB Fv in pancreatic beta cells developed more severe diabetes than their non-transgenic littermates, with earlier onset, faster diabetic processes, and higher mortality.