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BioMed Research International
Volume 2015 (2015), Article ID 102969, 11 pages
Research Article

Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

1Department of Pathology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki, Finland
2Children’s Hospital, University of Helsinki, 00290 Helsinki, Finland
3Department of Pathology, HUSLAB, Helsinki University Central Hospital, 05850 Hyvinkää, Finland
4Department of Pathology, HUSLAB, Helsinki University Central Hospital, 00290 Helsinki, Finland
5Laboratory Animal Centre, University of Helsinki, 00790 Helsinki, Finland
6Biomedicum Stem Cell Center, University of Helsinki, 00290 Helsinki, Finland

Received 8 August 2014; Revised 26 September 2014; Accepted 29 September 2014

Academic Editor: Monica Fedele

Copyright © 2015 Mervi E. Hyvönen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER) at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.