|
| Status |
Public on Sep 21, 2009 |
| Title |
The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Kidney |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology.
|
| |
|
| Overall design |
Two-Factor, Two-Level. AHRnull and wildtype mice were treated with dioxin (TCDD) or corn oil vehicle. 3 replicates per treatment for AHRnull mice, and 6 replicates per treatment for wildtype mice.
|
| |
|
| Contributor(s) |
Boutros PC, Miller M, Bielefeld KA, Pohjanvirta R, Harper PA |
| Citation(s) |
19759094 |
| |
| Submission date |
Apr 27, 2009 |
| Last update date |
Oct 19, 2012 |
| Contact name |
Paul C Boutros |
| E-mail(s) |
Paul.Boutros@utoronto.ca
|
| Organization name |
Ontario Institute for Cancer Research
|
| Street address |
101 College Street, Suite 800
|
| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5G 0A3 |
| Country |
Canada |
| |
|
| Platforms (1) |
| GPL8492 |
Affymetrix Mouse Genome 430 2.0 Array [CDF: Mm_ENTREZG_11.0.1] |
|
| Samples (18)
|
|
| This SubSeries is part of SuperSeries: |
| GSE15859 |
The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries |
|
| Relations |
| BioProject |
PRJNA123063 |
Less...
More...