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Glomerular Overproduction of Oxygen Radicals in Mpv17 Gene-Inactivated Mice Causes Podocyte Foot Process Flattening and Proteinuria

  • Focal segmental glomerulosclerosis is a steroid-resistant glomerular disease characterized by foot process flattening and heavy proteinuria. A similar disease was found to occur spontaneously in mice in which the Mpv17 gene was inactivated by retroviral insertion (Mpv17-/- mice). Here evidence is provided that glomerular damage in this murine model is due to overproduction of oxygen radicals and accumulation of lipid peroxidation adducts that were found in isolated glomeruli of Mpv17-/- mice. The development of glomerular disease in Mpv17-/- mice was inhibited by scavengers of oxygen radicals (dithiomethylurea) and lipid peroxidation (probucol), but not by steroid treatment. Although the glomerular polyanion was greatly reduced in proteinuric Mpv17-/- mice, it was preserved by antioxidative therapy. These results indicate that the glomerular disease in Mpv17-/- mice qualifies as a model of steroid-resistant focal segmental glomerulosclerosis and that experimental therapies with scavengers of oxygen radicals and lipid peroxidation efficiently ameliorate glomerular damage.

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Metadaten
Document Type:Article
Language:English
Parent Title (English):Am J Pathol. (The American Journal of Pathology)
Volume:154
Issue:4
First Page:1067
Last Page:1075
ISSN:0002-9440
DOI:https://doi.org/10.1016/S0002-9440(10)65359-X
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=10233845
Publisher:Elsevier
Publication year:1999
Departments, institutes and facilities:Institut für funktionale Gen-Analytik (IfGA)
Dewey Decimal Classification (DDC):500 Naturwissenschaften und Mathematik / 570 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Entry in this database:2018/09/21