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:Abstract. Ulcerative colitis (UC) is an intestinal disease characterized by chronic recurrent inflammation, but the underlying mechanism remains undefined and requires in-depth exploration. The aim of the present study was to investigate the biological effects of a small molecular compound M1002 of oxygen-sensing signaling pathway on dextran sulfate sodium (DSS)-induced intestinal inflammation colitis mouse models. It was found that the protective effects of M1002 on DSS-induced colitis. To determine how M1002 exerted its protective effect in DSS-induced colitis, we compared the global gene expression profiles in the gut between DSS control and M1002 treatment colitis mouse groups by RNA-Seq. The results demonstrated that HIF-1 signaling pathway-related genes were significantly upregulated in the gut of M1002 treatment colitis mice, whereas the Inflammatory bowel disease signaling pathway, the TNF signaling pathway, and Cytokines and inflammatory response signaling pathway related genes were significantly downregulated in the M1002 treatment group. 16S rRNA gene sequencing demonstrated remarkable variations in the composition of gut microbiota between DSS control and M1002 treatment colitis mice. Compared with DSS control colitis mice, the relative abundance of Eubacterium_nodatum and Halomonas in the gut microbiota was significantly increased at genus level in the gut of M1002 treatment colitis mice. Based on these findings, we tend to conclude that M1002 might alleviate DSS-induced gut injury in mice by regulation of HIF-1 signaling and up-regulating Eubacterium_nodatum and Halomonas.
Project description:In the DSS-induced colitis model, the epithelial damage and resulting inflammation is restricted to the colon, with a potential influence on the microbial composition in the adjacent cecum. Several studies have reported changes of the gut microbiota in the DSS-induced colitis model and other mouse models of IBD. Furthermore, metaproteomics analysis of the gut microbiome in a mouse model of Crohn’s disease demonstrated that disease severity and location are microbiota-dependent, with clear evidence for the causal role of bacterial dysbiosis in the development of chronic ileal inflammation. We have developed a refined model of chronic DSS-induced colitis that reflects typical symptoms of human IBD without a risky body weight loss usually observed in DSS models [Hoffmann et al., submitted]. In this study, we used metaproteomics to characterize the disease-related changes in bacterial protein abundance and function in the refined model of DSS-induced colitis. To assess the structural and functional changes, we applied 16S rRNA gene sequencing and metaproteomics analysis of the intestinal microbiota in three different entities of the intestinal environment, i.e. colon mucus, colon content and cecum content.
Project description:Ulcerative colitis (UC) is an intestinal pathology characterized by chronic recurrent inflammation, which requires in-depth exploration of its mechanisms. To investigate the biological effects of TLR2 on DSS-induced intestinal inflammation in mice, we constructed the WT and TLR2-KO colitis mice model. We found TLR2-KO mice were severely susceptible to DSS-induced colitis. To determine how TLR2 exerted a protective effect in DSS-induced colitis, we compared the global gene expression profiles in the gut between WT and TLR2-KO mice by RNA-Seq. Results suggested that cell cycle pathway-related genes were significantly downregulated in gut of TLR2-KO colitis mice. 16S rRNA gene sequencing demonstrated remarkable variation in the composition of gut microbiota between WT and TLR2-KO colitis mice. Compared with WT colitis mice, the relative abundance of Marinifilaceae, Rikenellaceae, Desulfovibrionaceae, Tannerellaceae, Ruminococcaceae, Clostridia, Mycoplasmataceae were significantly higher in the gut of TLR2-KO colitis mice at family level. Moreover, we found that the relative abundance of Marinifilaceae was negatively correlated with the expression of cell cycle signaling related genes by microbiome diversity-transcriptome collaboration analysis. We came to this conclusion: TLR 2-KO exacerbated DSS-induced intestinal injury by Marinifilaceae dependent attenuating cell cycle signaling.
Project description:A LINE-1 element, LIC105, was found in the Mus musculus domesticus inbred strain, C57BL/6J. Upon sequencing, this element was found to belong to a M. spretus LINE-1 subfamily originating within the last 0.2 million years. This is the second spretus-specific LINE-1 subfamily found to be represented in C57BL/6J. Although it is unclear how these M. spretus LINE-1s transferred from M. spretus to M. m. domesticus, it is now clear that at least two different spretus LINE-1 sequences have recently transferred. The limited divergence between the C57BL/6J spretus-like LINE-1s and their closest spretus ancestors suggests that the transfer did not involve an exceptionally long lineage of sequential transpositions.
Project description:Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD) with complex etiology involving chronic inflammation, immune dysregulation, and gut microbiota dysbiosis. Creatine, a natural nitrogenous com-pound, possesses anti-inflammatory and immunomodulatory properties, but its role in CAC remains unclear.We established an AOM/DSS-induced mouse model of CAC and supplemented mice with creatine. We assessed the effects of creatine on colitis severity, tumor burden, and histopathology. Additionally, we investigated the impact of crea-tine on gut barrier function, macrophage polarization, and gut microbiota composi-tion.Creatine supplementation significantly alleviated DSS-induced colitis, reduced tumor burden, and delayed CAC progression in mice. Mechanistically, creatine im-proved gut barrier function by protecting tight junction proteins from degradation in-duced by the modeling stimulus,influenced macrophage polarization, and main-tained gut microbiota diversity, promoting the abundance of beneficial bacteria while reducing harmful ones.Our findings suggest that creatine supplementation may rep-resent a promising supportive therapy for IBD and CAC by modulating the gut micro-biota and immune microenvironment. Further investigation is warranted to explore the clinical potential of creatine in the management of CAC.