Deletion of the G6pc2 Gene Encoding the Islet-Specific Glucose-6-Phosphatase Catalytic Subunit–Related Protein Does Not Affect the Progression or Incidence of

OBJECTIVE—Islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP), now known as G6PC2, is a major target of autoreactive T cells implicated in the pathogenesis of type 1 diabetes in both mice and humans. This study aimed to determine whether suppression of G6p2 gene expression might therefore prevent or delay disease progression. RESEARCH DESIGN AND METHODS—G6pc22/2 mice were generated on the NOD/ShiLtJ genetic background, and glycemia was monitored weekly up to 35 weeks of age to determine the onset and incidence of diabetes. The antigen specificity of CD8+ T cells infiltrating islets from NOD/ShiLtJ G6pc2+/+ and G6pc22/2 mice at 12 weeks was determined in parallel. RESULTS—The absence of G6pc2 did not affect the time of onset, incidence, or sex bias of type 1 diabetes in NOD/ShiLtJ mice. Insulitis was prominent in both groups, but whereas NOD