Glomerulopathy in the KK.Cg-Ay/J Mouse Reflects the Pathology of Diabetic Nephropathy
The KK.Cg-/J (KK-) mouse strain is a previously described model of type 2 diabetes with renal impairment. In the present study, female KK- mice received an elevated fat content diet (24% of calories), and a cohort was uninephrectomized (Unx) to drive renal disease severity. Compared to KK- controls,...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2013/498925 |
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| author | Stephen P. O'Brien Mandy Smith Hong Ling Lucy Phillips William Weber John Lydon Colleen Maloney Steven Ledbetter Cynthia Arbeeny Stefan Wawersik |
| author_facet | Stephen P. O'Brien Mandy Smith Hong Ling Lucy Phillips William Weber John Lydon Colleen Maloney Steven Ledbetter Cynthia Arbeeny Stefan Wawersik |
| author_sort | Stephen P. O'Brien |
| collection | DOAJ |
| description | The KK.Cg-/J (KK-) mouse strain is a previously described model of type 2 diabetes with renal impairment. In the present study, female KK- mice received an elevated fat content diet (24% of calories), and a cohort was uninephrectomized (Unx) to drive renal disease severity. Compared to KK- controls, 26-week-old KK- mice had elevated HbA1c, insulin, leptin, triglycerides, and cholesterol, and Unx further elevated these markers of metabolic dysregulation. Unx KK- mice also exhibited elevated serum BUN and reduced glomerular filtration, indicating that reduction in renal mass leads to more severe impairment in renal function. Glomerular hypertrophy and hypercellularity, mesangial matrix expansion, podocyte effacement, and basement membrane thickening were present in both binephric and uninephrectomized cohorts. Glomerular size was increased in both groups, but podocyte density was reduced only in the Unx animals. Consistent with functional and histological evidence of increased injury, fibrotic (fibronectin 1, MMP9, and TGFβ1) and inflammatory (IL-6, CD68) genes were markedly upregulated in Unx KK- mice, while podocyte markers (nephrin and podocin) were significantly decreased. These data suggest podocyte injury developing into glomerulopathy in KK- mice. The addition of uninephrectomy enhances renal injury in this model, resulting in a disease which more closely resembles human diabetic nephropathy. |
| format | Article |
| id | doaj-art-f3db8fd35b12472690d08ded295794ac |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-f3db8fd35b12472690d08ded295794ac2025-02-03T01:11:43ZengWileyJournal of Diabetes Research2314-67452314-67532013-01-01201310.1155/2013/498925498925Glomerulopathy in the KK.Cg-Ay/J Mouse Reflects the Pathology of Diabetic NephropathyStephen P. O'Brien0Mandy Smith1Hong Ling2Lucy Phillips3William Weber4John Lydon5Colleen Maloney6Steven Ledbetter7Cynthia Arbeeny8Stefan Wawersik9Tissue Protection and Repair, Genzyme, A Sanofi Company, 49 New York Ave., Framingham, MA 01701, USATissue Protection and Repair, Genzyme, A Sanofi Company, 49 New York Ave., Framingham, MA 01701, USATissue Protection and Repair, Genzyme, A Sanofi Company, 49 New York Ave., Framingham, MA 01701, USATissue Protection and Repair, Genzyme, A Sanofi Company, 49 New York Ave., Framingham, MA 01701, USATissue Protection and Repair, Genzyme, A Sanofi Company, 49 New York Ave., Framingham, MA 01701, USATissue Protection and Repair, Genzyme, A Sanofi Company, 49 New York Ave., Framingham, MA 01701, USATissue Protection and Repair, Genzyme, A Sanofi Company, 49 New York Ave., Framingham, MA 01701, USATissue Protection and Repair, Genzyme, A Sanofi Company, 49 New York Ave., Framingham, MA 01701, USATissue Protection and Repair, Genzyme, A Sanofi Company, 49 New York Ave., Framingham, MA 01701, USATissue Protection and Repair, Genzyme, A Sanofi Company, 49 New York Ave., Framingham, MA 01701, USAThe KK.Cg-/J (KK-) mouse strain is a previously described model of type 2 diabetes with renal impairment. In the present study, female KK- mice received an elevated fat content diet (24% of calories), and a cohort was uninephrectomized (Unx) to drive renal disease severity. Compared to KK- controls, 26-week-old KK- mice had elevated HbA1c, insulin, leptin, triglycerides, and cholesterol, and Unx further elevated these markers of metabolic dysregulation. Unx KK- mice also exhibited elevated serum BUN and reduced glomerular filtration, indicating that reduction in renal mass leads to more severe impairment in renal function. Glomerular hypertrophy and hypercellularity, mesangial matrix expansion, podocyte effacement, and basement membrane thickening were present in both binephric and uninephrectomized cohorts. Glomerular size was increased in both groups, but podocyte density was reduced only in the Unx animals. Consistent with functional and histological evidence of increased injury, fibrotic (fibronectin 1, MMP9, and TGFβ1) and inflammatory (IL-6, CD68) genes were markedly upregulated in Unx KK- mice, while podocyte markers (nephrin and podocin) were significantly decreased. These data suggest podocyte injury developing into glomerulopathy in KK- mice. The addition of uninephrectomy enhances renal injury in this model, resulting in a disease which more closely resembles human diabetic nephropathy.http://dx.doi.org/10.1155/2013/498925 |
| spellingShingle | Stephen P. O'Brien Mandy Smith Hong Ling Lucy Phillips William Weber John Lydon Colleen Maloney Steven Ledbetter Cynthia Arbeeny Stefan Wawersik Glomerulopathy in the KK.Cg-Ay/J Mouse Reflects the Pathology of Diabetic Nephropathy Journal of Diabetes Research |
| title | Glomerulopathy in the KK.Cg-Ay/J Mouse Reflects the Pathology of Diabetic Nephropathy |
| title_full | Glomerulopathy in the KK.Cg-Ay/J Mouse Reflects the Pathology of Diabetic Nephropathy |
| title_fullStr | Glomerulopathy in the KK.Cg-Ay/J Mouse Reflects the Pathology of Diabetic Nephropathy |
| title_full_unstemmed | Glomerulopathy in the KK.Cg-Ay/J Mouse Reflects the Pathology of Diabetic Nephropathy |
| title_short | Glomerulopathy in the KK.Cg-Ay/J Mouse Reflects the Pathology of Diabetic Nephropathy |
| title_sort | glomerulopathy in the kk cg ay j mouse reflects the pathology of diabetic nephropathy |
| url | http://dx.doi.org/10.1155/2013/498925 |
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