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Publication

Molecular Profiling of Diabetic Mouse Kidneys Reveals Novel Genes Linked to Glomerular Disease

Authors Katalin Susztak, Erwin Böttinger, Akiva Novetsky, Dan Liang, Yanqing Zhu, Emilio Ciccone, Dona Wu, Stephen Dunn, Peter McCue, Kumar Sharma Submitted By Kumar Sharma on 10/3/2003 Status Published Journal Diabetes Year 2004 Date Published 3/1/2004 Volume : Pages 53 : 784 - 794 PubMed Reference 14988265 Abstract One of the most serious complications of diabetes is the development of diabetic nephropathy, which leads to end-stage renal disease. Diabetic nephropathy of humans is characterized by the development of albuminuria and mesangial matrix expansion in the glomeruli. We performed microarray and phenotype analysis on kidneys from db/db mice (n=29), as a model of type 2 diabetes, streptozotocin-induced diabetic C57BL/6J (n=5), as model of type 1 diabetes and their non-diabetic controls (n=16) to describe gene expression changes that characterize the development of diabetic nephropathy. Statistical comparisons were implemented based on phenotypic outcome characteristics of the animals. Neighborhood supervised analytical methods (1) was used to find genes, whose expression can classify samples based on the presence or absence of mesangial matrix expansion, the best indicator for the development of end-stage renal disease. We identified hydroxysteroid dehydrogenase 3beta isotype 4 (Hsd3b4) and osteopontin, as lead classifier genes in relation to the mesangial matrix expansion phenotype. The expression levels of these genes in the kidney were able to classify animals based on the absence or presence of diabetic glomerulopathy also in a separate group of diabetic mice with high degree of precision. Immunohistochemical analysis of murine and human diabetic kidney samples showed that both markers were specifically expressed in podocytes in the glomeruli and followed similar regulation as observed in the microarray. The application of statistical modeling approaches based on phenotype has led to the identification of new markers for diabetic kidney disease and introduces novel hypotheses regarding the pathogenesis of diabetic nephropathy.

Investigators with authorship
Name Institution Erwin Bottinger Mount Sinai School of Medicine Kumar Sharma University of California San Diego

Complications
All ComplicationsBioinformatics BoneCardiomyopathy CardiovascularGastro-Intestinal (GI) NephropathyNeuropathy & Neurocognition Pediatric Endocrinology Retinopathy UropathyWound Healing

Genes
Symbol Description Spp1 secreted phosphoprotein 1