NOD.Idd9.3.Tnfrsf9-/- mice carry a C57BL/10SnJ-derived genome on Chromosome 4 containing the Idd9.3 region. The Idd9.3 (insulin dependent diabetes susceptibility 9.3) region contains 15 genes, including the candidate gene Tnfrsf9 (tumor necrosis factor receptor superfamily, member 9 and commonly referred to as 4-1BB or Cd137). In addition, the C57BL/10SnJ-derived Tnfrsf9 allele (within the congenic region) is altered using by a zinc finger nuclease (ZFN)-mediated two base pair insertion in the second coding exon resulting in a premature stop codon. Mice homozygous for the congenic region (and the Tnfrsf9 knock-out) are viable and fertile. Tnfrsf9 encodes a receptor that contributes to the clonal expansion, survival, and development of T cells. Compared to C57BL/10Sn, the NOD-derived Tnfrsf9 allele is hypofunctional. NOD.Idd9.3 mice develop higher levels of CD137+ and FOXP3+ regulatory T cells and serum soluble CD137. They are resistant to type 1 diabetes (T1D). NOD.Idd9.3.Tnfrsf9-/- mice do not express CD137 on CD8+ T cells and are resistant to diabetes.

NOD.Idd9.3.Tnfrsf9-/- mice contain the C57BL/10SnJ-derived Idd9.3 (insulin dependent diabetes susceptibility 9.3) region that includes the Tnfrsf9 (tumor necrosis factor receptor superfamily, member 9) gene modified to contain a 2 bp insertion resulting in a premature stop codon. Mice homozygous for the congenic region (and the Tnfrsf9 knock-out) are resistant to Type 1 diabetes.

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