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Csf2 and Ptgs2 Epigenetic Dysregulation in Diabetes-prone Bicongenic B6.NODC11bxC1tb Mice
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 th...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Libertas Academica
2015
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603573/ https://www.ncbi.nlm.nih.gov/pubmed/26512207 http://dx.doi.org/10.4137/GEG.S29696 |
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| author | Garrigan, Erin Belkin, Nicole S. Seydel, Federica Han, Zhao Carter, Jamal 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. |
| author_facet | Garrigan, Erin Belkin, Nicole S. Seydel, Federica Han, Zhao Carter, Jamal 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. |
| author_sort | Garrigan, Erin |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-4603573 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2015 |
| publisher | Libertas Academica |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-46035732015-10-28 Csf2 and Ptgs2 Epigenetic Dysregulation in Diabetes-prone Bicongenic B6.NODC11bxC1tb Mice Garrigan, Erin Belkin, Nicole S. Seydel, Federica Han, Zhao Carter, Jamal 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. Genet Epigenet Original Research 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. Libertas Academica 2015-10-11 /pmc/articles/PMC4603573/ /pubmed/26512207 http://dx.doi.org/10.4137/GEG.S29696 Text en © 2015 the author(s), publisher and licensee Libertas Academica Ltd. This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License. |
| spellingShingle | Original Research Garrigan, Erin Belkin, Nicole S. Seydel, Federica Han, Zhao Carter, Jamal 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. Csf2 and Ptgs2 Epigenetic Dysregulation in Diabetes-prone Bicongenic B6.NODC11bxC1tb Mice |
| title | Csf2 and Ptgs2 Epigenetic Dysregulation in Diabetes-prone Bicongenic B6.NODC11bxC1tb Mice |
| title_full | Csf2 and Ptgs2 Epigenetic Dysregulation in Diabetes-prone Bicongenic B6.NODC11bxC1tb Mice |
| title_fullStr | Csf2 and Ptgs2 Epigenetic Dysregulation in Diabetes-prone Bicongenic B6.NODC11bxC1tb Mice |
| title_full_unstemmed | Csf2 and Ptgs2 Epigenetic Dysregulation in Diabetes-prone Bicongenic B6.NODC11bxC1tb Mice |
| title_short | Csf2 and Ptgs2 Epigenetic Dysregulation in Diabetes-prone Bicongenic B6.NODC11bxC1tb Mice |
| title_sort | csf2 and ptgs2 epigenetic dysregulation in diabetes-prone bicongenic b6.nodc11bxc1tb mice |
| topic | Original Research |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603573/ https://www.ncbi.nlm.nih.gov/pubmed/26512207 http://dx.doi.org/10.4137/GEG.S29696 |
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