E-GEOD-10117 - Murine Spleen: Wild type vs Brx haploinsufficiency

Status
Released on 9 February 2009, last updated on 1 May 2014
Organism
Mus musculus
Samples (12)
Array (1)
Protocols (6)
Description
Comaprison of the gene expression profiles of the spleen between wild type and Brx haploinsuffieint mice Nuclear factor of activated T-cells 5 (NFAT5) is a transcription factor that regulates hyperosmolarity-responsive genes and helps activated T lymphocytes adapt to and discharge their functions in hyperosmolar environments. We report here that the Rho-type guanine nucleotide exchange factor (GEF) Brx is essential for increased NFAT5 expression in response to osmotic stress in lymphoid tissues. Indeed, brx haploinsufficient mice expressed significantly less NFAT5 in their spleens than wild type controls and their splenocytes had a defective response to osmotic stress in vitro. Haploinsufficient mice also had smaller-sized spleens containing fewer splenocytes, as well as a defective immunoglobulin response to ovalbumin compared to wild type mice. The Brx GEF domain and the p38 mitogen-activated kinase (MAPK) cascade were both required for osmotic stress-mediated induction of NFAT5 in Jurkat cells. Brx physically interacted with the cJun kinase (JNK)-interacting protein (JIP) 4, a scaffold protein for activation of the p38 MAPK cascade that was required for osmotic stress-induced NFAT5 expression. Thus, Brx is a signal integrator for the adaptive response to osmotic stress in the immune system, activating small G proteins, attracting JIP4 and stimulating p38 MAPK, ultimately increasing the expression of NFAT5 and activating hyperosmolarity protective genes, a phenomenon crucial for proper immune function in hyperosmolar environments, such as inflammatory sites and immune organs. Keywords: Genetic modification Two-condition experiment: Wild type and Brx haploinsuffient, 3 replicates, labeling swap for each
Experiment type
transcription profiling by array 
Contacts
Tomoshige Kino <kinot@mail.nih.gov>, Manoli Irini, Yan A Su, Yonghong Wang
Citation
Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5. Kino T, Takatori H, Manoli I, Wang Y, Tiulpakov A, Blackman MR, Su YA, Chrousos GP, DeCherney AH, Segars JH. , Europe PMC 19211510
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-10117.idf.txt
Sample and data relationshipE-GEOD-10117.sdrf.txt
Raw data (1)E-GEOD-10117.raw.1.zip
Processed data (1)E-GEOD-10117.processed.1.zip
Array designA-GEOD-6356.adf.txt
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