title: Deletion of the G6pc2 gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein does not affect the progression or incidence of type 1 diabetes in NOD/ShiLtJ mice.
abstract: 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.
  
  
  METHODS
  G6pc2(-/-) 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 G6pc2(-/-) 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/ShiLtJ G6pc2(+/+) islets contained CD8(+) T cells reactive to the G6pc2 NRP peptide, G6pc2 NRP-reactive T cells were absent in NOD/ShiLtJ G6pc2(-/-) islets.
  
  
  CONCLUSIONS
  These results demonstrate that G6pc2 is an important driver for the selection and expansion of islet-reactive CD8(+) T cells infiltrating NOD/ShiLtJ islets. However, autoreactivity to G6pc2 is not essential for the emergence of autoimmune diabetes. The results remain consistent with previous studies indicating that insulin may be the primary autoimmune target, at least in NOD/ShiLtJ mice.
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: James K
authors: JK
authors: Oeser
authors: Vrajesh V
authors: VV
authors: Parekh
authors: Yingda
authors: Y
authors: Wang
authors: Naresh K
authors: NK
authors: Jegadeesh
authors: Suparna A
authors: SA
authors: Sarkar
authors: Randall
authors: R
authors: Wong
authors: Catherine E
authors: CE
authors: Lee
authors: Lynley D
authors: LD
authors: Pound
authors: John C
authors: JC
authors: Hutton
authors: Luc
authors: L
authors: Van Kaer
authors: Richard M
authors: RM
authors: O'Brien
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D020134:Catalytic Domain; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D005952:Glucose-6-Phosphatase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D001323:Autoantibodies; D011506:Proteins; D005952:Glucose-6-Phosphatase; C117983:G6pc2 protein, mouse