publication . Article . 2011

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

James K. Oeser; Vrajesh V. Parekh; Yingda Wang; Naresh K. Jegadeesh; Suparna A. Sarkar; Randall Wong; Catherine E. Lee; Lynley D. Pound; John C. Hutton; Luc Van Kaer; ...
Open Access English
  • Published: 01 Oct 2011 Journal: Diabetes, volume 60, issue 11, pages 2,922-2,927 (issn: 0012-1797, eissn: 1939-327X, Copyright policy)
  • Publisher: American Diabetes Association
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. RESEARCH DESIGN AND 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 we...
Subjects
free text keywords: Immunology and Transplantation, Internal Medicine, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, medicine, Biology, Nod, Islet, geography.geographical_feature_category, geography, Type 1 diabetes, medicine.disease, Autoantibody, Endocrinology, medicine.medical_specialty, Diabetes mellitus, CD8, Insulitis
Funded by
NIH| The Role of IGRP in the Pathogenesis of Type 1 Diabetes
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01DK076027-01
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
,
NIH| Diabetes Research and Training Center
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5P60DK020593-25
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
,
NIH| MULTIDISCIPLINARY TRAINING IN MOLECULAR ENDOCRINOLOGY
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2T32DK007563-11
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
,
NIH| Cloning of molecular targets of Cell Mediated Autoimmunity in Type 1 Diabetes
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01DK052068-12
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
,
NIH| UCHSC DIABETES ENDOCRINOLOGY RESEARCH CENTER
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5P30DK057516-04
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
22 references, page 1 of 2

1 Hutton JC O’Brien RM Glucose-6-phosphatase catalytic subunit gene family. J Biol Chem 2009;284:29241–29245 19700406 [OpenAIRE] [PubMed]

2 Wang Y Martin CC Oeser JK Deletion of the gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen results in a mild metabolic phenotype. Diabetologia 2007;50:774–778 17265032 [PubMed]

3 Bouatia-Naji N Rocheleau G Van Lommel L A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels. Science 2008;320:1085–1088 18451265 [OpenAIRE] [PubMed]

4 Chen WM Erdos MR Jackson AU Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. J Clin Invest 2008;118:2620–2628 18521185 [OpenAIRE] [PubMed]

5 Lieberman SM Evans AM Han B Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes. Proc Natl Acad Sci USA 2003;100:8384–8388 12815107 [OpenAIRE] [PubMed]

6 Tsai S Shameli A Santamaria P CD8+ T cells in type 1 diabetes. Adv Immunol 2008;100:79–124 19111164 [OpenAIRE] [PubMed]

7 Mukherjee R Wagar D Stephens TA Lee-Chan E Singh B Identification of CD4+ T cell-specific epitopes of islet-specific glucose-6-phosphatase catalytic subunit-related protein: a novel beta cell autoantigen in type 1 diabetes. J Immunol 2005;174:5306–5315 15843527 [PubMed]

8 Yang J Danke NA Berger D Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects. J Immunol 2006;176:2781–2789 16493034 [OpenAIRE] [PubMed]

9 Jarchum I Nichol L Trucco M Santamaria P DiLorenzo TP Identification of novel IGRP epitopes targeted in type 1 diabetes patients. Clin Immunol 2008;127:359–365 18358785 [OpenAIRE] [PubMed]

10 Takaki T Marron MP Mathews CE HLA-A*0201-restricted T cells from humanized NOD mice recognize autoantigens of potential clinical relevance to type 1 diabetes. J Immunol 2006;176:3257–3265 16493087 [OpenAIRE] [PubMed]

11 Han B Serra P Amrani A Prevention of diabetes by manipulation of anti-IGRP autoimmunity: high efficiency of a low-affinity peptide. Nat Med 2005;11:645–652 15908957 [PubMed]

12 Serreze DV Chapman HD Varnum DS B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new “speed congenic” stock of NOD.Ig mu null mice. J Exp Med 1996;184:20 49–2053 8920894 [OpenAIRE] [PubMed]

13 Takaki T Lieberman SM Holl TM Requirement for both H-2Db and H-2Kd for the induction of diabetes by the promiscuous CD8+ T cell clonotype AI4. J Immunol 2004;173:2530–2541 15294969 [OpenAIRE] [PubMed]

14 Lieberman SM Takaki T Han B Santamaria P Serreze DV DiLorenzo TP Individual nonobese diabetic mice exhibit unique patterns of CD8+ T cell reactivity to three islet antigens, including the newly identified widely expressed dystrophia myotonica kinase. J Immunol 2004;173:6727–6734 15557165 [OpenAIRE] [PubMed]

15 Bluestone JA Herold K Eisenbarth G Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 2010;464:1293–1300 20432533 [OpenAIRE] [PubMed]

22 references, page 1 of 2
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. RESEARCH DESIGN AND 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 we...
Subjects
free text keywords: Immunology and Transplantation, Internal Medicine, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, medicine, Biology, Nod, Islet, geography.geographical_feature_category, geography, Type 1 diabetes, medicine.disease, Autoantibody, Endocrinology, medicine.medical_specialty, Diabetes mellitus, CD8, Insulitis
Funded by
NIH| The Role of IGRP in the Pathogenesis of Type 1 Diabetes
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01DK076027-01
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
,
NIH| Diabetes Research and Training Center
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5P60DK020593-25
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
,
NIH| MULTIDISCIPLINARY TRAINING IN MOLECULAR ENDOCRINOLOGY
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2T32DK007563-11
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
,
NIH| Cloning of molecular targets of Cell Mediated Autoimmunity in Type 1 Diabetes
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01DK052068-12
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
,
NIH| UCHSC DIABETES ENDOCRINOLOGY RESEARCH CENTER
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5P30DK057516-04
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
22 references, page 1 of 2

1 Hutton JC O’Brien RM Glucose-6-phosphatase catalytic subunit gene family. J Biol Chem 2009;284:29241–29245 19700406 [OpenAIRE] [PubMed]

2 Wang Y Martin CC Oeser JK Deletion of the gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen results in a mild metabolic phenotype. Diabetologia 2007;50:774–778 17265032 [PubMed]

3 Bouatia-Naji N Rocheleau G Van Lommel L A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels. Science 2008;320:1085–1088 18451265 [OpenAIRE] [PubMed]

4 Chen WM Erdos MR Jackson AU Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. J Clin Invest 2008;118:2620–2628 18521185 [OpenAIRE] [PubMed]

5 Lieberman SM Evans AM Han B Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes. Proc Natl Acad Sci USA 2003;100:8384–8388 12815107 [OpenAIRE] [PubMed]

6 Tsai S Shameli A Santamaria P CD8+ T cells in type 1 diabetes. Adv Immunol 2008;100:79–124 19111164 [OpenAIRE] [PubMed]

7 Mukherjee R Wagar D Stephens TA Lee-Chan E Singh B Identification of CD4+ T cell-specific epitopes of islet-specific glucose-6-phosphatase catalytic subunit-related protein: a novel beta cell autoantigen in type 1 diabetes. J Immunol 2005;174:5306–5315 15843527 [PubMed]

8 Yang J Danke NA Berger D Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects. J Immunol 2006;176:2781–2789 16493034 [OpenAIRE] [PubMed]

9 Jarchum I Nichol L Trucco M Santamaria P DiLorenzo TP Identification of novel IGRP epitopes targeted in type 1 diabetes patients. Clin Immunol 2008;127:359–365 18358785 [OpenAIRE] [PubMed]

10 Takaki T Marron MP Mathews CE HLA-A*0201-restricted T cells from humanized NOD mice recognize autoantigens of potential clinical relevance to type 1 diabetes. J Immunol 2006;176:3257–3265 16493087 [OpenAIRE] [PubMed]

11 Han B Serra P Amrani A Prevention of diabetes by manipulation of anti-IGRP autoimmunity: high efficiency of a low-affinity peptide. Nat Med 2005;11:645–652 15908957 [PubMed]

12 Serreze DV Chapman HD Varnum DS B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new “speed congenic” stock of NOD.Ig mu null mice. J Exp Med 1996;184:20 49–2053 8920894 [OpenAIRE] [PubMed]

13 Takaki T Lieberman SM Holl TM Requirement for both H-2Db and H-2Kd for the induction of diabetes by the promiscuous CD8+ T cell clonotype AI4. J Immunol 2004;173:2530–2541 15294969 [OpenAIRE] [PubMed]

14 Lieberman SM Takaki T Han B Santamaria P Serreze DV DiLorenzo TP Individual nonobese diabetic mice exhibit unique patterns of CD8+ T cell reactivity to three islet antigens, including the newly identified widely expressed dystrophia myotonica kinase. J Immunol 2004;173:6727–6734 15557165 [OpenAIRE] [PubMed]

15 Bluestone JA Herold K Eisenbarth G Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 2010;464:1293–1300 20432533 [OpenAIRE] [PubMed]

22 references, page 1 of 2
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publication . Article . 2011

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

James K. Oeser; Vrajesh V. Parekh; Yingda Wang; Naresh K. Jegadeesh; Suparna A. Sarkar; Randall Wong; Catherine E. Lee; Lynley D. Pound; John C. Hutton; Luc Van Kaer; ...