Gene expression profiling of mature CD4 SP thymocytes from a mouse strain with an ENU-induced mutation in Zfp335. Mus musculus

The generation of naïve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a naïve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation. Overall design: WT and blt/blt mature CD4SP thymocytes were sorted from mixed hematopoietic chimeras for RNA extraction and gene expression analysis on Affymetrix arrays. 6 samples were analyzed in total, with 3 biological replicates per genotype.