The Albert Einstein College of Medicine (AECOM), the Thomas Jefferson University (TJU) and the University of Minnesota (UMINN) propose to form a member unit of the consortium to develop mouse models for diabetic complications. We propose to contribute mouse models that we have available. In addition, we propose to develop and examine a number of new models for diabetic nephropathy. The Albert Einstein College of Medicine provides Transgenic and Knockout Core Facilities, and Microarray Facilities providing high-density microarrays of cDNA inserts and oligonucleotide arrays. AECOM?s and Philadelphia?s NIH designated Diabetes Research and Training Centers (DRTC) provide other core facilities, including Radioimmunoassay Core, Biochemical Physiology Core and Macromolecular Structure Core that are important phenotyping assets for the proposed work. The AECOM barrier facility where the mice will be developed and housed allow maintenance and breeding of mice in a pathogen-free facility, making it possible to easily ship mice to other facilities. Infrastructure at TJU includes a barrier facility where mice will be made diabetic and a robust histopathology with outstanding expertise on both human and mouse diabetic nephropathy. We have generated/characterized mice with mutations in Lepr (db mutant leptin synaptopodin, Dcn (decorin), and MnSOD (manganese superoxide dismutase). We now propose to validate some of these models. We will generate new transgenic lines to challenge existing models with pathophysiologic genetic modifications in cellular glucose uptake, mitochondrial oxidant injury, podocyte homeostasis, and TGFb activity. We will characterize and validate these models using advanced histopathology and morphometry and gene expression profiling based on microarray technology. Since many of these perturbations are expected to promote diabetic complications in other tissue types as well, it is possible that combining our gene modifications with those developed by other members of the consortium may provide for novel models of range of diabetic complications in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK060995-05
Application #
6935183
Study Section
Special Emphasis Panel (ZDK1-GRB-4 (O2))
Program Officer
Ketchum, Christian J
Project Start
2001-09-30
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
5
Fiscal Year
2004
Total Cost
$822,894
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Qi, Haiying; Casalena, Gabriella; Shi, Shaolin et al. (2017) Glomerular Endothelial Mitochondrial Dysfunction Is Essential and Characteristic of Diabetic Kidney Disease Susceptibility. Diabetes 66:763-778
Zhao, Jinghong; Miyamoto, Satoshi; You, Young-Hyun et al. (2015) AMP-activated protein kinase (AMPK) activation inhibits nuclear translocation of Smad4 in mesangial cells and diabetic kidneys. Am J Physiol Renal Physiol 308:F1167-77
Declèves, Anne-Emilie; Zolkipli, Zarazuela; Satriano, Joseph et al. (2014) Regulation of lipid accumulation by AMP-activated kinase [corrected] in high fat diet-induced kidney injury. Kidney Int 85:611-23
Sweiss, Natalie; Sharma, Kumar (2014) Adiponectin effects on the kidney. Best Pract Res Clin Endocrinol Metab 28:71-9
Dutta, Dipankar J; Zameer, Andleeb; Mariani, John N et al. (2014) Combinatorial actions of Tgf? and Activin ligands promote oligodendrocyte development and CNS myelination. Development 141:2414-28
Casalena, Gabriela; Krick, Stefanie; Daehn, Ilse et al. (2014) Mpv17 in mitochondria protects podocytes against mitochondrial dysfunction and apoptosis in vivo and in vitro. Am J Physiol Renal Physiol 306:F1372-80
Daehn, Ilse; Casalena, Gabriella; Zhang, Taoran et al. (2014) Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis. J Clin Invest 124:1608-21
Börgeson, Emma; Sharma, Kumar (2013) Obesity, immunomodulation and chronic kidney disease. Curr Opin Pharmacol 13:618-24
You, Young-Hyun; Okada, Shinichi; Ly, San et al. (2013) Role of Nox2 in diabetic kidney disease. Am J Physiol Renal Physiol 304:F840-8
Shi, Shaolin; Yu, Liping; Zhang, Taoran et al. (2013) Smad2-dependent downregulation of miR-30 is required for TGF-?-induced apoptosis in podocytes. PLoS One 8:e75572

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