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Series GSE6789 Query DataSets for GSE6789
Status Public on Mar 30, 2007
Title response to IL-1b of WT and IRAK4 kinase dead mouse embryonic fibroblasts
Organism Mus musculus
Experiment type Expression profiling by array
Summary IRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Though regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function is still controversial. In order to investigate the role of IRAK-4 kinase function in vivo, ‘knock-in’ mice were generated by replacing the wild type IRAK-4 gene with a mutant gene encoding kinase deficient IRAK-4 protein (IRAK-4 KD). Analysis of embryonic fibroblasts and macrophages obtained from IRAK-4 KD mice with a number of experimental techniques demonstrated that they greatly lack responsiveness to stimulation with IL-1b or a Toll-like receptor 7 (TLR7) agonist. One of the techniques used, microarray analysis, identified IRAK-4 kinase-dependent IL-1b response genes in mouse embryonic fibroblasts and revealed that the induction of IL-1b-responsive mRNAs was largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in IL-1R/TLR7-mediated induction of inflammatory responses.
Keywords: genetic modification, strain comparison, cell stimulation, time course, inflammatory response
Overall design The response of mouse embryonic fibroblasts from WT and IRAK4 kinase dead animals to stimulation with IL-1b at two time points was determined. There were 12 samples in total, 6 from WT and 6 from IRAK4 kinase dead cells; for each strain there were 3 conditions: growth for 4 hours without stimulation (the strain-specific control), growth for 1 hour with stimulation, and growth for 4 hours with stimulation; for each condition there were two biological replicates.
Contributor(s) Koziczak-Holbro M, Gram H, Kinzel B, Glueck A, Hartmann N, Letzkus M
Citation(s) 17337443
Submission date Jan 18, 2007
Last update date Feb 11, 2019
Contact name Anton Glück
Organization name Novartis Institutes for BioMedical Research
Street address WSJ-386.13.50
City Basel
ZIP/Postal code 4002
Country Switzerland
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (12)
GSM155304 MEFs_unstimulated_4hours_rep1
GSM156795 WT-MEFs_unstimulated_4hours_rep2
GSM156796 WT-MEFs_IL1b-stimulated_1hour_rep1
BioProject PRJNA99223

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Supplementary file Size Download File type/resource
GSE6789_RAW.tar 42.9 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file

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