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Development of an inducible and reversible mouse model of podocyte effacement

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dc.contributor.advisor Jones, Nina Stringer, Colin D.M. 2011-08-31T20:25:58Z 2011-08-31T20:25:58Z 2011-08 2011-08-26 2011-08-31
dc.description.abstract Podocytes are specialized epithelial cells which wrap glomerular capillaries with numerous interdigitating foot processes (FP). Between adjacent FPs a unique junction, the slit diaphragm (SD), functions as the final blood filtration barrier. Actin organization is critical for maintaining FP structure and SD function, and the adaptor protein Nck can bind an intracellular SD component to couple it with actin regulators. Podocyte-specific deletion of Nck in mice results in proteinuria and FP effacement. To better understand FP remodelling, we have pursued a transgenic mouse model utilizing an inducible and reversible dominant negative Nck (DN-Nck) to prevent signalling to actin regulators, exclusively in podocytes. Effects of DN-Nck were first confirmed in vitro, and transgenic mice were then generated and induced to express DN-Nck. Despite obtaining several mice which exhibited a mild renal phenotype, transgene expression appeared to be lost in successive generations. Full in vivo analysis awaits generation of additional transgenic founders. en_US
dc.language.iso en en_US
dc.subject nephropathy en_US
dc.subject proteinuria en_US
dc.subject glomerular filtration en_US
dc.subject podocyte en_US
dc.subject slit diaphragm en_US
dc.subject Nck en_US
dc.subject transgenic mouse model en_US
dc.title Development of an inducible and reversible mouse model of podocyte effacement en_US
dc.type Thesis en_US Molecular and Cellular Biology en_US Master of Science en_US Department of Molecular and Cellular Biology en_US
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