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Home > Phenotyping and Pathophysiology > Kidney Injury Core > Chronic Injury (non-diabetic) > NEP25 TG mice (podocyte injury)

Selective Podocyte Injury using NEP25 transgenic mice. This is a mouse model of acquired glomerular sclerosis that allows induction of podocyte injury in a manner in which onset and severity can be controlled (4). A transgenic mouse strain (NEP25) expresses human CD25 selectively in podocytes (under the control of the nephrin promoter).



NEP25 TG mice (podocyte injury) > Protocol Section

To induce podocyte damage, the mice are injected with anti-Tac (Fv)-PE38 (LMB2), an immunotoxin that binds specifically to human CD25. The mice develop progressive nonselective proteinuria, ascites, and edema. The podocytes show foot process effacement, vacuolar degeneration, detachment and downregulation of synaptopodin, WT-1, nephrin, and podocalyxin. Mesangial cells show matrix expansion, increased collagen, mesangiolysis, and, progressive sclerosis. Parietal epithelial cells show vacuolar degeneration and proliferation, and endothelial cells are swollen (4). In addition to inducibility, this model has the additional advantage that the severity of the glomerular injury can be controlled by varying the dose of LMB2 administered.

Publications for NEP25 TG mice (podocyte injury) (1)

Matsusaka T, Xin J, Niwa S, Kobayashi K, Akatsuka A, Hashizume H, Wang QC, Pastan I, Fogo AB, Ichikawa I. Genetic engineering of glomerular sclerosis in the mouse via control of onset and severity of podocyte-specific injury. J Am Soc Nephrol (2005) 16:1013-23
View abstract View in PubMed

This study aimed to generate a mouse model of acquired glomerular sclerosis. A model system that allows induction of podocyte injury in a manner in which onset and severity can be controlled was designed. A transgenic mouse strain (NEP25) that expresses human CD25 selectively in podocytes was first generated. Injection of anti-Tac (Fv)-PE38 (LMB2), an immunotoxin with specific binding to human CD25, induced progressive nonselective proteinuria, ascites, and edema in NEP25 mice. Podocytes showed foot process effacement, vacuolar degeneration, detachment and downregulation of synaptopodin, WT-1, nephrin, and podocalyxin. Mesangial cells showed matrix expansion, increased collagen, mesangiolysis, and, later, sclerosis. Parietal epithelial cells showed vacuolar degeneration and proliferation, whereas endothelial cells were swollen. The severity of the glomerular injury was LMB2 dose dependent. With 1.25 ng/g body wt or more, NEP25 mice developed progressive glomerular damage and died within 2 wk. With 0.625 ng/g body wt of LMB2, NEP25 mice survived >4 wk and developed focal segmental glomerular sclerosis. Thus, the study has established a mouse model of acquired progressive glomerular sclerosis in which onset and severity can be preprogrammed by experimental maneuvers.

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Last updated on 2007-02-06 Moderated by Raymond Harris