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Using CRISPR to knockout three arms of the interferon system in NOD mice

Using CRISPR to knockout three arms of the interferon system in NOD mice

PhD project

Deficiency of either IFNg or IFNa receptors does not dramatically influence diabetes in NOD mice, whereas deficiency of STAT1, the transcription factor downstream of all interferons, or treatment with JAK inhibitors, protects NOD mice from developing diabetes. To study whether interferons have overlapping roles in the pathogenesis of diabetes, we generated NOD mice with deficiency in all three of the interferon receptors (Ifnar1, Ifngr1 and Ifnlr1). Remarkably, NOD mice lacking all three receptors were not protected from autoimmune diabetes, with only a slight delay in onset. Mice lacking all three receptors had significantly less insulitis than wild-type mice, even very close to the onset of diabetes, suggesting that the limited immune infiltration in the islet is more pathogenic than in wild-type NOD mice. We are now testing the hypothesis that deletion of interferon receptors results in loss of regulation of pathogenic T cells.

Supervised by:

  • A/Prof Helen Thomas
  • Dr Tom Brodnicki
  • Disease Focus:

  • Type 1 diabetes
  • Research Unit:

  • Islet biology