Project description:This study determined the genes that are differentially expressed when regulatory T cells (Tregs) were isolated from the lamina propria of the small and large intestine from mice with impaired IL-2Rβ signaling (designated Y3) or impaired IL-2Rβ signaling and lack of CD103 expression (designated Y3/CD103-/-) when compared to Tregs from WT mice. 204 unique annotated mRNAs were differentially expressed by ≥1.5 fold between these 3 groups (Fig. 6B). Very few mRNAs were uniquely up or down regulated in relationship to impaired IL-2Rβ signaling or the combination of impaired IL-2Rβ signaling and lack of CD103 expression. Thus, lack of CD103 does not obviously regulated signaling in Tregs in the gut mucosa and most differentially expressed genes were due to impaired IL_2Rβ signaling. Gene enrichment analysis of these differentially expressed genes identified 4 major enrichment groups (EG) are: EG1, Cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway; EG2, regulation of lymphocyte activation and proliferation; EG3, regulation of cell death and the caspase pathway in apoptosis; and EG4, transcription. Mouse regulatory T cells (Tregs) cells were FACS purified based on expression of red fluorescent protein linked to the Foxp3 gene. These cells were obtained from the lamina propria of the small and large intestine from WT, Y3, and Y3/CD103-/- mice. Total RNA was prepared and processed to probe Affymetrix mouse Gene ST2.0 arrays.
Project description:This study determined the genes that are differentially expressed when regulatory T cells (Tregs) were isolated from the lamina propria of the small and large intestine from mice with impaired IL-2Rβ signaling (designated Y3) or impaired IL-2Rβ signaling and lack of CD103 expression (designated Y3/CD103-/-) when compared to Tregs from WT mice. 204 unique annotated mRNAs were differentially expressed by ≥1.5 fold between these 3 groups (Fig. 6B). Very few mRNAs were uniquely up or down regulated in relationship to impaired IL-2Rβ signaling or the combination of impaired IL-2Rβ signaling and lack of CD103 expression. Thus, lack of CD103 does not obviously regulated signaling in Tregs in the gut mucosa and most differentially expressed genes were due to impaired IL_2Rβ signaling. Gene enrichment analysis of these differentially expressed genes identified 4 major enrichment groups (EG) are: EG1, Cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway; EG2, regulation of lymphocyte activation and proliferation; EG3, regulation of cell death and the caspase pathway in apoptosis; and EG4, transcription.
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:Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before the acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin and hepatic cell necrosis. Moreover, LcS alleviated the acetaminophen-induced intestinal mucosal permeability, elevation in serum IL-1α and lipopolysaccharide, and decreased levels of serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol and sugars in the gut. Additionally, the transcriptome and proteomics showed that LcS mitigated the downregulation of metabolism and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.
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.
Project description:The aim of the study was to investigate whether the trefoil peptide genes, in concerted action with a miRNA regulatory network, were contributing to nutritional maintrenance. Using a Tff2 knock-out mouse model, 48 specific miRNAs were noted to be significantly deregulated when compared to the wild type strain.
Project description:The aim of the study was to investigate whether the trefoil peptide genes, in concerted action with a miRNA regulatory network, were contributing to nutritional maintrenance. Using a Tff3 knock-out mouse model, 21 specific miRNAs were noted to be significantly deregulated when compared to the wild type strain.
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.