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.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OGU.10214/2935 |
| Date | 31 August 2011 |
| Creators | Stringer, Colin D.M. |
| Contributors | Jones, Nina |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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