Hudkins, Kelly L. and Pichaiwong, Warangkana and Wietecha, Tomasz and Kowalewska, Jolanta and Banas, Miriam C. and Spencer, Min W. and Muehlfeld, Anja and Koelling, Mariko and Pippin, Jeffrey W. and Shankland, Stuart J. and Askari, Bardia and Rabaglia, Mary E. and Keller, Mark P. and Attie, Alan D. and Alpers, Charles E. (2010) BTBR Ob/Ob Mutant Mice Model Progressive Diabetic Nephropathy. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 21 (9). pp. 1533-1542. ISSN 1046-6673,
Full text not available from this repository. (Request a copy)Abstract
There remains a need for robust mouse models of diabetic nephropathy (DN) that mimic key features of advanced human DN. The recently developed mouse strain BTBR with the ob/ob leptin-deficiency mutation develops severe type 2 diabetes, hypercholesterolemia, elevated triglycerides, and insulin resistance, but the renal phenotype has not been characterized. Here, we show that these obese, diabetic mice rapidly develop morphologic renal lesions characteristic of both early and advanced human DN. BTBR ob/ob mice developed progressive proteinuria beginning at 4 weeks. Glomerular hypertrophy and accumulation of mesangial matrix, characteristic of early DN, were present by 8 weeks, and glomerular lesions similar to those of advanced human DN were present by 20 weeks. By 22 weeks, we observed an approximately 20% increase in basement membrane thickness and a >50% increase in mesangial matrix. Diffuse mesangial sclerosis (focally approaching nodular glomerulosclerosis), focal arteriolar hyalinosis, mesangiolysis, and focal mild interstitial fibrosis were present. Loss of podocytes was present early and persisted. In summary, BTBR ob/ob mice develop a constellation of abnormalities that closely resemble advanced human DN more rapidly than most other murine models, making this strain particularly attractive for testing therapeutic interventions.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ARTERIAL-BLOOD PRESSURE; PODOCYTE NUMBER; GLOMERULAR INJURY; KNOCKOUT MICE; MOUSE MODELS; MURINE MODEL; LEPTIN; SUSCEPTIBILITY; EXPRESSION; OBESITY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2020 06:41 |
| Last Modified: | 15 Jul 2020 06:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24264 |
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