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Series GSE9037 Query DataSets for GSE9037
Status Public on Jun 25, 2008
Title response to LPS of WT and IRAK4 kinase dead mouse bone marrow macrophages
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 bone marrow macrophages obtained from WT and IRAK-4 KD mice with a number of experimental techniques demonstrated that the IRAK-4 KD cells greatly lack responsiveness to stimulation with the Toll-like receptor 4 (TLR4) agonist LPS. One of the techniques used, microarray analysis, identified IRAK-4 kinase-dependent LPS response genes and revealed that the induction of LPS-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 TLR4-mediated induction of inflammatory responses.
Keywords: genetic modification, strain comparison, cell stimulation, time course, anti-bacterial response, innate immune response, inflammatory response
 
Overall design The response of mouse bone marrow macrophages from WT and IRAK4 kinase dead animals to stimulation with LPS 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) 18266302
Submission date Sep 13, 2007
Last update date Aug 02, 2019
Contact name Anton Glück
E-mail(s) anton.glueck@novartis.com
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)
GSM229589 WT_BoneMarrowMacrophages_unstimulated_4hours_rep1
GSM229590 WT_BoneMarrowMacrophages_unstimulated_4hours_rep2
GSM229591 WT_BoneMarrowMacrophages_LPS-stimulated_1hour_rep1
Relations
BioProject PRJNA102541

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Supplementary file Size Download File type/resource
GSE9037_RAW.tar 42.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
Raw data provided as supplementary file

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