Glucocorticoid (GC) stimulation of both branching morphogenesis and cytodifferentiation in the developing lung is mediated by the Glucocorticoid Receptor (GR). Seventy-five percent of mice homozygous for a targeted disruption of the GR gene (GR hypo) die shortly after birth due to respiratory failure. Surviving GRhypo mice are normal and fertile. We used Differential Display Reverse Transcription PCR (DD-PCR) and then cDNA microarrays to identify differentially expressed genes in GR hypo compared to wildtype mice. The retinoic acid responsive gene, midkine (MK) was up-regulated in GRhypo mice at fetal day 18 and at neonatal day 1 (in both survivors and non-survivors). At fetal day 16.5, MK was down-regulated in GRhypo mice compared to wildtype. GC treatment up-regulated MK expression in fetal day 20 rat lung Epi cells in primary culture. These results indicate that in the absence of GR, MK is disregulated in the lung: in the pseudoglandular and canalicular stage, MK is down-regulated, but by the saccular stage, and then shortly after birth, the absence of GR results in up-regulation of MK expression. Our findings suggest that down-regulation of the growth factor MK in late gestation is essential to normal terminal differentiation of the fetal lung.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33736 |
| Date | January 2002 |
| Creators | Comber, Julie. |
| Contributors | Kaplan, Feige (advisor) |
| 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: 001864575, proquestno: MQ78853, Theses scanned by UMI/ProQuest. |
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