Autosomal dominant polycystic kidney disease (PKD) is caused by mutations of the PKD1 or PKD2 genes. Cyst cells exhibit sustained expression of fetal genes such as PAX2. Normally, PAX2 is involved in kidney development and is rapidly downregulated after birth. Overactivity of the canonical beta-catenin signaling pathway has also been linked to the formation of renal cysts. To determine whether beta-catenin activity is linked to the level of PAX2 expression in vivo, we created a transgenic mouse overexpressing PAX2 in mature proximal tubules of the kidney. Here we report that the canonical beta-catenin signaling activity is increased in mice bearing the targeted PAX2 transgene. / There is also evidence that non-canonical Writ signaling may be involved in the development of renal cysts but this pathway is uncharacterized. We therefore studied the ontogeny of a downstream marker of this pathway (NFAT) and its localization in the developing kidney. Here we report that NFAT activity is high in early stages of kidney development and is rapidly downregulated at birth. The NFAT signal is diffuse and is expressed in both mesenchymal and epithelial cells of the developing kidney.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.84066 |
| Date | January 2005 |
| Creators | Patenaude, Anne-Marie |
| Publisher | McGill University |
| 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 | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Human Genetics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002261446, proquestno: AAIMR22758, Theses scanned by UMI/ProQuest. |
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