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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 29, 2019 |
| Title |
Establishing dose-strain specific transcriptomic changes in murine models of TCDD-induced toxicity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are known to cause a wide range of toxicities. The consequences of acute exposure to TCDD in rodents, and to a lesser degree in humans, can range from mild chloracne to terminal illness, such as cancer. The aryl hydrocarbon receptor (AHR) plays a critical role in mediating the toxic effects of TCDD. However, the underlying mechanism of differential sensitivities to TCDD across organisms remain poorly understood, however differences in the AHR are known to play a role. To further investigate this, we profiled the transcriptomic responses in liver from TCDD sensitive or resistant mice, 19 hours following exposure to either 5 or 500 μg/kg TCDD. Analysis of transcriptomic profiles revealed several key findings: 1) TCDD sensitive C57BL/6 mice demonstrated an increased number of changes within the hepatic transcriptome than the TCDD resistant DBA/2 mice following exposure to low dose (5 μg/kg) TCDD, but this balanced out at the high dose (500 μg/kg), and the transcriptome from ratonized mice showed more changes than either C57BL/6 or DBA/2, regardless of dose; 2) mRNA abundance of the ‘AHR-core’ battery of genes was consistently perturbed in dioxin sensitive mice (C57BL/6 and rWT) in comparison to dioxin resistant mice (DBA/2), with Inmt showing significant changes in transcription only in the ratonized mouse liver and Cyp1a2 more response in non-transgenic mice (C57BL/6 and DBA/2); 3) a small subset of genes had significantly altered transcription in either the TCDD-resistant DBA/2 mouse liver (including Rpl18a, Mbd6, Onecut2 and Lipg) or the TCDD-sensitive cohorts (C57BL/6 and rWT; including Smcp, Acpp, Acot2 and Acot3). Overall, our results demonstrate considerable TCDD-induced transcriptomic differences between DBA/2 and C57BL/6 mouse lines.
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| Overall design |
Adult male DBA/2 and C57BL/6 mice and transgenic rWT mice were treated by gavage with 0, 5, or 500 µg/kg TCDD dissolved in corn oil vehicle. Mice were euthanized 19 hours following treatment and liver tissue was harvested for analysis. RNA was isolated and the transcriptome for each animal assayed on separate microarrays.
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| Contributor(s) |
Lee SS, Prokopec SD, Sun RX, Yao CQ, Watson JD, Pohjanvirta R, Boutros PC |
| Citation(s) |
31511937 |
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| Submission date |
Feb 26, 2019 |
| Last update date |
Oct 31, 2019 |
| Contact name |
Stephenie Prokopec |
| E-mail(s) |
stephenie.prokopec@oicr.on.ca
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| Organization name |
Ontario Institute for Cancer Research
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| Street address |
661 University Avenue, Suite 510
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5G 0A3 |
| Country |
Canada |
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| Platforms (2) |
| GPL24557 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [CDF: mogene20st_Mm_ENTREZG_22] |
| GPL26227 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] [CDF: mogene11st_Mm_ENTREZG_22.0.0] |
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| Samples (34)
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| Relations |
| BioProject |
PRJNA524352 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE127217_RAW.tar |
219.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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