Project description:It is known that ubiquitination is important for T cell receptor (TCR) signaling during T cell activation but the breadth of ubiquitination events triggered during TCR signaling is not completely understood. This dataset utilizes di-glycine remnant profiling combined with mass spectrometry to identify a global landscape of ubiquitination events downstream of the TCR and to quantify changes ubiquitin abundance in response to TCR stimulation. Additionally, whole cell proteomics data were generated to measure protein abundances during TCR stimulation. Mouse primary T cells were isolated, proliferated and either remained resting or stimulated with CD3/CD28 to activate downstream signaling through the TCR and co-stimulatory pathways. Di-glycine remnant profiling and whole cell proteomics was performed on rested cells and cells that had undergone CD3/CD28 TCR stimulation for 4 hours. These data were analyzed to identify the ubiquitination events during TCR activation and to quantify the change in peptide-based ubiquitin abundance and total protein abundance over the course of the 4 hour TCR stimulation. Integration of di-glycine and whole cell proteomics was used to generate protein-specific predictions of whether ubiquitination events downstream of TCR signaling lead to a decrease in associated protein abundance. The analysis of these data suggests that T cell activation leads to an increase in ubiquitination that is not associated with proteasomal or lysosomal degradation.
Project description:We created mice, which are deficient for Myc specifically in cardiac myocytes by crossing crossed Myc-floxed mice (Mycfl/fl) and MLC-2VCre/+ mice. Serial analysis of earlier stages of gestation revealed that Myc-deficient mice died prematurely at E13.5-14.5. Morphological analyses of E13.5 Myc-null embryos showed normal ventricular size and structure; however, decreased cardiac myocyte proliferation and increased apoptosis was observed. BrdU incorporation rates were also decreased significantly in Myc-null myocardium. Myc-null mice displayed a 3.67-fold increase in apoptotic cardiomyocytes by TUNEL assay. We examined global gene expression using oligonucleotide microarrays. Numerous genes involved in mitochondrial death pathways were dysregulated including Bnip3L and Birc2. Keywords: wildtype vs Myc-null
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.
Project description:The regulation of thymocyte development by RNA-binding proteins (RBPs) is largely unexplored. We identified 642 RBPs in the thymus and focused on Arpp21, which shows selective and dynamic expression in early thymocytes. Arpp21 was downregulated in response to T cell receptor (TCR) and Ca2+ signals. Downregulation required Stim1/Stim2 and CaMK4 expression and involved Arpp21 protein phosphorylation, polyubiquitination and proteasomal degradation. Arpp21 directly bound RNA through its R3H domain, with a preference for uridine-rich motifs, promoting the expression of target mRNAs. Analysis of the Arpp21-bound transcriptome revealed strong interactions with the Rag1 3'-UTR. Arpp21-deficient thymocytes showed reduced Rag1 expression, delayed TCR rearrangement and a less diverse TCR repertoire. This phenotype was recapitulated in Rag1 3'-UTR mutant mice harboring a deletion of the Arpp21 response region. These findings show how thymocyte-specific Arpp21 promotes Rag1 expression to enable TCR repertoire diversity until signals from the TCR terminate Arpp21 and Rag1 activities.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.