Project description:Tumor necrosis factor-associated factors 2 and 3 (TRAF2 and TRAF3) were shown to function in a co-operative and non-redundant manner to suppress nuclear factor-κB2 (NF-κB2) activation, gene expression and survival in mature B cells. In the absence of this suppressive activity, B cells developed independently of the obligatory B cell survival factor, BAFF (B cell activating factor of the tumor necrosis factor family). This constitutive, lineage-specific suppression of B cell survival by TRAF2 and TRAF3 determines the requirement for BAFF to sustain B cell development in vivo. We wished to investigate the effect on gene expression in B cells which lacked the negative regulators TRAF2 and TRAF3, and hence had hyperactive NF-kB2 signalling. As Baff-tg mice display a similar phenotype, and have a genetic modification which acts in the same pathway, yet further up, than TRAF2 and TRAF3, we wished to compare and contrast Baff-tg B cells with TRAF2 and TRAF3 deficient B cells. This analysis should identify genes that are important in B cell survival. Experiment Overall Design: Lymph node B cells were purified from Traf2 B cell knockout mice, Traf3 B cell knockout mice, Baff-tg mice and respective controls. RNA was extracted and hybridised to Affymetrix 430 2.0 Mouse Genome Arrays. Samples were processed and hence analysed on three spearate days. Day 1 two control mice: Traf2lox/lox pool and CD19-cretg were compared to two knockout mice: Traf2DB 80 and Traf3DB 94. On Day 2 three control mice: Traf2lox/lox 77, Traf2lox/lox 79 and Traf3lox/lox 97 were compared to two knockout mice: Traf2DB 76 and Traf3DB 01. On Day 3 three control mice: WT33, WT34, WT35 were compared to three Baff-tg mice: Baff-tg 99, Baff-tg 100, Baff-tg 101.
Project description:Tumor necrosis factor-associated factors 2 and 3 (TRAF2 and TRAF3) were shown to function in a co-operative and non-redundant manner to suppress nuclear factor-κB2 (NF-κB2) activation, gene expression and survival in mature B cells. In the absence of this suppressive activity, B cells developed independently of the obligatory B cell survival factor, BAFF (B cell activating factor of the tumor necrosis factor family). This constitutive, lineage-specific suppression of B cell survival by TRAF2 and TRAF3 determines the requirement for BAFF to sustain B cell development in vivo. We wished to investigate the effect on gene expression in B cells which lacked the negative regulators TRAF2 and TRAF3, and hence had hyperactive NF-kB2 signalling. As Baff-tg mice display a similar phenotype, and have a genetic modification which acts in the same pathway, yet further up, than TRAF2 and TRAF3, we wished to compare and contrast Baff-tg B cells with TRAF2 and TRAF3 deficient B cells. This analysis should identify genes that are important in B cell survival. Keywords: Genetic modification
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.