Epithelial cells of the mammalian intestine are covered with a mucus layer that prevents direct contact with intestinal microbes but also constitutes a substrate for mucus-degrading bacteria. To study the effect of mucus degradation on the host response, germ-free mice were colonized with Akkermansia muciniphila. This anaerobic bacterium belonging to the Verrucomicrobia is specialized in the degradation of mucin, the glycoprotein present in mucus, and found in high numbers in the intestinal tract of human and other mammalian species. Efficient colonization of A. muciniphila was observed with highest numbers in the cecum, where most mucin is produced. In contrast, following colonization by Lactobacillus plantarum, a facultative anaerobe belonging to the Firmicutes that ferments carbohydrates, similar cell-numbers were found at all intestinal sites. Whereas A. muciniphila was located closely associated with the intestinal cells, L. plantarum was exclusively found in the lumen. The global transcriptional host response was determined in intestinal biopsies and revealed a consistent, site-specific, and unique modulation of about 750 genes in mice colonized by A. muciniphila and over 1500 genes after colonization by L. plantarum. Pathway reconstructions showed that colonization by A. muciniphila altered mucosal gene expression profiles toward increased expression of genes involved in immune responses and cell fate determination, while colonization by L. plantarum led to up-regulation of lipid metabolism. These indicate that the colonizers induce host responses that are specific per intestinal location. In conclusion, we propose that A. muciniphila modulates pathways involved in establishing homeostasis for basal metabolism and immune tolerance toward commensal microbiota.
Modulation of Mucosal Immune Response, Tolerance, and Proliferation in Mice Colonized by the Mucin-Degrader Akkermansia muciniphila.
Sex, Specimen part
View SamplesMicroarray analysis was performed on BWF1 mice spleenocyte cells in control and pCONS treated mice.
Distinct gene signature revealed in white blood cells, CD4(+) and CD8(+) T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide.
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View SamplesDown syndrome is the most common form of genetic mental retardation. How Trisomy 21 causes mental retardation remains unclear and its effects on adult neurogenesis have not been addressed. To gain insight into the mechanisms causing mental retardation we used microarrays to investigate gene expression differences between Ts1Cje (a mouse model of Down syndrome) and C57BL/6 littermate control neurospheres. The neurospheres were generated from neural stem cells and progenitors isolated from the lateral walls of the lateral ventricles from adult mice.
Gene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome.
Sex, Disease
View SamplesThe aim of the present study was to compare, on a statistical basis, the performance of different microarray platforms to detect differences in gene expression in a realistic and challenging biological setting. Gene expression profiles in the hippocampus of five wild-type and five transgenic C-doublecortin-like kinase mice were evaluated with five microarray platforms: Applied Biosystems, Affymetrix, Agilent, Illumina and home-spotted oligonucleotide arrays. We observed considerable overlap between the different platforms, the overlap being better detectable with significance level-based ranking than with a p-value based cut-off. Confirming the qualitative agreement between platforms, Pathway analysis consistently demonstrated aberrances in GABA-ergic signalling in the transgenic mice, even though pathways were represented by only partially overlapping genes on the different platforms.
Can subtle changes in gene expression be consistently detected with different microarray platforms?
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View SamplesThe goal of this study was to identify the molecular characteristics and putative markers distinguishing IL-10eGFP+CD138hi and IL-10eGFP-CD138hi plasmocytes. To this end, IL-10eGFP B-green mice were challenged intravenously with Salmonella typhimurium (strain SL7207, 10e7 CFU), and IL-10eGFP+CD138hi as well as IL-10eGFP-CD138hi plasmocytes were isolated from the spleen on the next day. For this, single cell suspensions were prepared, cells were treated with Fc block (10 g/ml, anti-CD16/CD32, clone 2.4G2), and then stained with an antibody against CD138 conjugated to PE (1/400; from BD Pharmingen) followed by incubation with anti-PE microbeads (Miltenyi Biotech). CD138+ cells were then enriched on Automacs (Miltenyi Biotech) using the program possel_d2. Cells were then stained with anti-CD19-PerCP, anti-CD138-PE, and antibodies against CD11b, CD11c, and TCR conjugated to APC as a dump channel to exclude possible contaminants. DAPI was added to exclude dead cells. Live IL-10eGFP+CD138hi and IL-10eGFP-CD138hi cells were subsequently isolated on a cell sorter. The purity of the samples was always above 98%. This led to the identification of LAG-3 as a cell surface receptor specifically expressed on IL-10eGFP+CD138hi cells but not on IL-10eGFP-CD138hi cells.
LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells.
Sex, Specimen part
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