Glucocorticoid (GC) signalling via the GC receptor (GR) regulates many aspects of lung development. To determine the need for epithelial GC-GR signalling, triple transgenic (TT) mice with doxycycline (dox) – inducible suppression of GR exclusively in the distal lung epithelium (DLE) were created. Following exposure to dox, E18.5 TT fetuses showed a reduction in GR mRNA levels and elimination of GR protein expression exclusively in the DLE. Newborn TT pups had decreased viability and TT fetal lungs had increased tissue to airspace ratios, decreased levels of proximal epithelial protein CC10, of all surfactant proteins (ATII cell proteins), of ion conductance channels β and γENaC, of water channel AQP5, and of ATI cell protein T1α. Thus DLE GC-GR signalling is important for neonatal viability and increased mortality of TT pups could be due to impaired epithelial differentiation, leading to decreased surfactant protein expression, delayed fluid clearance and/or increased lung cellularity.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/17697 |
| Date | 22 September 2009 |
| Creators | Manwani, Neetu |
| Contributors | Sweezey, Neil |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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