Goldwich, Andreas and Steinkasserer, Alexander and Gessner, Andre and Amann, Kerstin (2012) Impairment of podocyte function by diphtheria toxin-a new reversible proteinuria model in mice. LABORATORY INVESTIGATION, 92 (12). pp. 1674-1685. ISSN 0023-6837,
Full text not available from this repository. (Request a copy)Abstract
Diphtheria toxin (DTx) receptor (DTR)-mediated conditional cell ablation in transgenic mice is a powerful tool to analyze cell function in vivo. Transgenic mice with cell-specific expression of the human DTR have been developed that allow conditional depletion of these cells in vivo through administration of the toxin. We have performed a careful analysis of mice after DTx injection and found an unexpected side effect. Treatment of wild-type C57BL/6 mice with DTx leads to a marked transient and completely reversible proteinuria, as a consequence of podocyte dysfunction that is morphologically characterized by foot process fusion and detachment from the glomerular basal membrane. In vitro analysis displayed that DTx-treated podocytes show diminished attachment to basal membrane proteins. Five to 9 days after DTx application the mice recover completely. Glomerular proteinuria is a hallmark of glomerular disease due to dysfunction of the filtration barrier. Rodents have been extensively used experimentally to better define the mechanisms of disease induction and progression. However, nongenetic mouse models of proteinuric glomerular damage are limited and display various shortcomings. We suggest DTx-induced transient kidney dysfunction as a new reversible model of experimental podocyte injury, which could be used as an additional approach to complement studies in human. Laboratory Investigation (2012) 92, 1674-1685; doi:0.1038/labinvest.2012.133; published online 24 September 2012
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BOVINE SERUM-ALBUMIN; IN-VIVO DEPLETION; DENDRITIC CELLS; MOUSE MODEL; MEMBRANOUS NEPHROPATHY; NEPHROTIC-SYNDROME; TRANSGENIC MOUSE; T-CELLS; RECEPTOR; KIDNEY; diphtheria toxin; mouse model; podocytes; proteinuria; slit membrane |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 May 2020 05:08 |
| Last Modified: | 04 May 2020 05:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17633 |
Actions (login required)
 |
View Item |
