Obstruction of the urinary tract activates apoptotic pathways in collecting duct cells and leads to loss of renal parenchyma prior to surgical intervention. It has been suggested that development molecular programs may be reactivated to offset acute organ damage. One such molecule, Pax-2, is expressed throughout the fetal collecting duct and was recently shown to suppress apoptosis during kidney development. / We hypothesized that during urinary tract obstruction (UTO), PAX-2 expression is reactivated in the mature kidney, partially suppressing apoptosis; and that mice with PAX-2 mutations will have increased susceptibility to parenchymal damage during UTO. / Wildtype (C3H) and heterozygous PAX-2 mutant mice (C3H/ PAX-21Neu) underwent unilateral ureteral ligation or sham operation at six weeks of age. Kidneys were removed, weighed and assayed for Pax-2 reactivation following 5, 10 and 15 days of UTO. Kidneys were then screened for apoptosis by TUNEL staining, and the novel anti-cleaved spectrin assay. / Pax-2 protein expression fell to nearly undetectable levels in the first weeks of life but was sharply reactivated in collecting duct cells of wildtype, but not in PAX-21Neu mutant mice with 10 days of UTO. Wildtype mice with UTO had increased TUNEL, cleaved spectrin and reduced kidney weight after 10-15 days UTO. Mutant mice had exaggerated increases in TUNEL staining, cleaved spectrin and parenchymal loss in the obstructed kidney. / In conclusion, we have shown that PAX-2 is highly expressed in the fetal kidney but is normally down regulated in the postnatal period; it is rapidly reactivated in collecting duct cells during UTO. Mice with genetically limited PAX-2 expression have heightened susceptibility to apoptosis and renal parenchymal loss following acute UTO.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.81615 |
| Date | January 2005 |
| Creators | Cohen, Tiffany J. |
| 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 (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002198817, proquestno: AAIMR12418, Theses scanned by UMI/ProQuest. |
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