Tonic Signaling Controls Gene Expression in T Lymphocytes. Mus musculus

To determine the role of tonic signals through the adapter LAT in controling helper T cell function, we performed microarray analysis of splenic CD4+ T cells from mice that are WT for LAT, are deficient in LAT (KO), and have a point-mutated version of LAT that abrogates PLCg1 binding (Y136F). These mouse models allow for inducible perturbation or deletion of LAT (using floxed alleles and the Cre-ER system), so we compared gene expression after both 1 and 4 weeks of tamoxifen treatment. We identified a cluster of genes that are downregulated when LAT is perturbed, and these genes are also putative targets of the histone deacetylase HDAC7. We explored this mechanistic link between LAT, HDAC7, and genes in this cluster in CD4+ T cells Overall design: Mice that are CRE ER+ and either LAT WT, LAT f/- (KO), or LAT Y136F/- were treated with tamoxifen for 1 or 4 weeks to inducibly delete or point-mutate LAT. Naïve CD44low CD4+ T cells were sorted from mouse spleens from three mice per genotype and analyzed by Agilent Mouse GE 4x44k arrays.