Project description:NGS analysis of BCR IGVH regions in wild type (WT) and TCL1 transgenic mice with intact (TCL1 Nfat2+/+) and deleted (TCL1 Nfat2-/-) NFAT2 expression
Project description:Chronic lymphocytic leukemia (CLL) is a disorder of mature B cells. Most patients are characterized by indolent disease and an anergic phenotype of their leukemia cells which refers to a state of unresponsiveness to B cell receptor stimulation. Using the Eµ-TCL1 mouse model, we show that B cell-specific ablation of NFAT2 leads to the loss of the anergic phenotype culminating in a significantly compromised life expectancy and histological transformation to aggressive disease. We further define a gene expression signature of anergic CLL cells consisting of several NFAT2-dependant genes employing microarray technology.
Project description:Analysis of the effect of CLL development on differentation and gene expression of splenic monocytes. C57BL/6 mice were transplanted with murine CLL cells from Eµ-TCL1 mice and after 6 weeks total RNA was isolated from splenic monocytes from leukemic mice and matched WT controls.
Project description:Tcl1 is known to be involved in survival, proliferation and differentiation of human lymphocytes and mouse embryonic stem cells. Loss of Tcl1 gene in the KO mouse model affects skin integrity inducing alopecia and ulcerations. The study used epidermal keratinocytes from wild type (WT), Tcl1 knock down (KO) and K14-driven TCL1 transgenic (TGKO) mouse models to investigate the role of Tcl1 gene in the skin homeostasis. Our data indicate that Tcl1 loss mainly induces a decrease in the gene expression of keratinocytes, which is largely rescued by K14-TCL1. GO analysis revealed Tcl1 to be involved in the proliferation and differentiation of mouse keratinocytes. Moreover, pathway analysis identifies growth factor and MAPK signaling to be highly implicated.