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
Erwin BottingerMount Sinai School of Medicine
Kumar SharmaUniversity of California San Diego


Spp1secreted phosphoprotein 1