Csf2 and Ptgs2 epigenetic dysregulation in diabetesprone bicongenic B6.NODC11bxC1tb mice

Erin Garrigan, Nicole S. Belkin, Federica Seydel, Zhao Han, Jamal H. Carter, Marcia McDuffie, Laurence Morel, Ammon B. Peck, Michael J. Clare-Salzler, Mark Atkinson, Clive Wasserfall, Abdoreza Davoodi-Semiromi, Jing Da Shi, Carrie Haskell-Luevano, Li Jun Yang, John J. Alexander, Autumn Cdebaca, Teresa Piliant, Corin Riggs, Matthew Amick & 2 others Sally A. Litherland, R. Bober

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

In Type 1 diabetic (T1D) human monocytes, STAT5 aberrantly binds to epigenetic regulatory sites of two proinflammatory genes, CSF2 (encoding granulocyte-macrophage colony-stimulating factor) and PTGS2 (encoding prostaglandin synthase 2/cyclooxygenase 2). Bicongenic B6.NOD C11bxC1tb mice re-create this phenotype of T1D monocytes with only two nonobese diabetic (NOD) Idd subloci (130.8 Mb-149.7 Mb, of Idd5 on Chr 1 and 32.08-53.85 Mb of Idd4.3 on Chr11) on C57BL/6 genetic background. These two Idd loci interact through STAT5 binding at upstream regulatory regions affecting Csf2 (Chr 11) and Ptgs2 (Chr 1) expression. B6.NODC11bxC1tb mice exhibited hyperglycemia and immune destruction of pancreatic islets between 8 and 30 weeks of age, with 12%-22% penetrance. Thus, B6.NODC11bxC1tb mice embody NOD epigenetic dysregulation of gene expression in myeloid cells, and this defect appears to be sufficient to impart genetic susceptibility to diabetes in an otherwise genetically nonautoimmune mouse.

Original languageEnglish (US)
Pages (from-to)5-17
Number of pages13
JournalGenetics and Epigenetics
Volume1
Issue number7
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Inbred NOD Mouse
Gene encoding
Nucleic Acid Regulatory Sequences
Cyclooxygenase 2
Granulocyte-Macrophage Colony-Stimulating Factor
Prostaglandin-Endoperoxide Synthases
Medical problems
Epigenomics
Gene expression
Monocytes
Defects
Penetrance
Myeloid Cells
Genetic Predisposition to Disease
Islets of Langerhans
Hyperglycemia
Phenotype
Gene Expression
Genes
Genetic Background

Keywords

  • Autoimmune
  • Congenic mice
  • Cytokine
  • Diabetes
  • Epigenetic gene regulation
  • Inflammation

ASJC Scopus subject areas

  • Biochemistry
  • Genetics

Cite this

Csf2 and Ptgs2 epigenetic dysregulation in diabetesprone bicongenic B6.NODC11bxC1tb mice. / Garrigan, Erin; Belkin, Nicole S.; Seydel, Federica; Han, Zhao; Carter, Jamal H.; McDuffie, Marcia; Morel, Laurence; Peck, Ammon B.; Clare-Salzler, Michael J.; Atkinson, Mark; Wasserfall, Clive; Davoodi-Semiromi, Abdoreza; Shi, Jing Da; Haskell-Luevano, Carrie; Yang, Li Jun; Alexander, John J.; Cdebaca, Autumn; Piliant, Teresa; Riggs, Corin; Amick, Matthew; Litherland, Sally A.; Bober, R.

In: Genetics and Epigenetics, Vol. 1, No. 7, 01.01.2015, p. 5-17.

Research output: Contribution to journalArticle

Garrigan, E, Belkin, NS, Seydel, F, Han, Z, Carter, JH, McDuffie, M, Morel, L, Peck, AB, Clare-Salzler, MJ, Atkinson, M, Wasserfall, C, Davoodi-Semiromi, A, Shi, JD, Haskell-Luevano, C, Yang, LJ, Alexander, JJ, Cdebaca, A, Piliant, T, Riggs, C, Amick, M, Litherland, SA & Bober, R 2015, 'Csf2 and Ptgs2 epigenetic dysregulation in diabetesprone bicongenic B6.NODC11bxC1tb mice', Genetics and Epigenetics, vol. 1, no. 7, pp. 5-17. https://doi.org/10.4137/GEG.S29696
Garrigan, Erin ; Belkin, Nicole S. ; Seydel, Federica ; Han, Zhao ; Carter, Jamal H. ; McDuffie, Marcia ; Morel, Laurence ; Peck, Ammon B. ; Clare-Salzler, Michael J. ; Atkinson, Mark ; Wasserfall, Clive ; Davoodi-Semiromi, Abdoreza ; Shi, Jing Da ; Haskell-Luevano, Carrie ; Yang, Li Jun ; Alexander, John J. ; Cdebaca, Autumn ; Piliant, Teresa ; Riggs, Corin ; Amick, Matthew ; Litherland, Sally A. ; Bober, R. / Csf2 and Ptgs2 epigenetic dysregulation in diabetesprone bicongenic B6.NODC11bxC1tb mice. In: Genetics and Epigenetics. 2015 ; Vol. 1, No. 7. pp. 5-17.
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AU - Han, Zhao

AU - Carter, Jamal H.

AU - McDuffie, Marcia

AU - Morel, Laurence

AU - Peck, Ammon B.

AU - Clare-Salzler, Michael J.

AU - Atkinson, Mark

AU - Wasserfall, Clive

AU - Davoodi-Semiromi, Abdoreza

AU - Shi, Jing Da

AU - Haskell-Luevano, Carrie

AU - Yang, Li Jun

AU - Alexander, John J.

AU - Cdebaca, Autumn

AU - Piliant, Teresa

AU - Riggs, Corin

AU - Amick, Matthew

AU - Litherland, Sally A.

AU - Bober, R.

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