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| Status |
Public on May 02, 2017 |
| Title |
HF001-A: Gene expression patterns in the progression towards canine copper-associated chronic hepatitis |
| Organism |
Canis lupus familiaris |
| Experiment type |
Expression profiling by array
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| Summary |
Copper is an essential trace element, but can become toxic when present in abundance. The severe effects of copper-metabolism imbalance are illustrated by the inherited disorders Wilson disease and Menkes disease. The Labrador retriever dog breed is a novel non-rodent model for copper-storage defects displaying identical phenotypic alterations and carrying mutations in genes known to be involved in copper transport. Besides disease initiation and progression of copper accumulation, the molecular mechanisms and pathways involved in copper accumulation and eventually progression towards copper associated chronic hepatitis still remains unclear. Using liver tissue of Labrador retrievers in different stages of copper-associated hepatitis, expression levels targeted at candidate genes as well as transcriptome microarrays, have shed light on involved molecular pathways. At the initial phase, viz. increased hepatic copper levels, transcriptomic alterations in livers revealed enrichment for cell adhesion, developmental, inflammatory, and cytoskeleton pathways. Upregulation of targeted MT1A and COMMD1 mRNA shows the livers first response to rising intrahepatic copper concentrations. In livers with copper-associated hepatitis mainly an activation of inflammatory pathways is detected. Once the hepatitis is in the chronic stage, transcriptional differences are found in cell adhesion adaptations and cytoskeleton remodelling. In view of the high similarities in hepatopathies between men and dog extrapolation of these dog data into human biomedicine seems feasible.
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| Overall design |
Canine Gene Expression Microarrays V1 (Agilent Technologies, Belgium) representing 42,034 canine 60-mer probes in a 4x44K layout were used. The experiment was carried out in dye swap set-up in 18 Labrador retriever dogs (N: n=4, HC: n=5, HCH: n=4, HCCH: n=5, random samples per group). As reference material a pool of 10 healthy dogs were used. N: normal liver; HC: high copper group; HCH: high copper hepatitis group; HCCH: high copper chronic hepatitis group.
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| Contributor(s) |
Dirksen K, Spee B, Penning LC, van den Ingh TS, Burgener IA, Watson AL, Groot Koerkamp M, Rothuizen J, van Steenbeek FG, Fieten H |
| Citation(s) |
28459846 |
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| Submission date |
Sep 14, 2016 |
| Last update date |
May 04, 2017 |
| Contact name |
Marian Groot Koerkamp |
| Organization name |
Princess Maxima Center for Pediatric Oncology
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| Department |
Research
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| Lab |
Drostlab
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| Street address |
Heidelberglaan 25
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| City |
Utrecht |
| State/province |
Utrecht |
| ZIP/Postal code |
3584 CS |
| Country |
Netherlands |
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| Platforms (1) |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA343021 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE86932_RAW.tar |
67.7 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE86932_normalized_data.txt.gz |
20.1 Mb |
(ftp)(http) |
TXT |
| GSE86932_protocols.xls.gz |
10.0 Kb |
(ftp)(http) |
XLS |
| Processed data are available on Series record |
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