Gene expression profiling of PBMC from petstore mice, C57Bl/6 laboratory mice, and C57Bl/6 laboratory mice cohoused with petstore
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE78979 | GEO | 2016/03/09
SECONDARY ACCESSION(S): PRJNA314572
REPOSITORIES: GEO
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Project description:Transcriptional analysis of immunological characteristics of petstore mice, C57Bl/6 laboratory mice, and C57Bl/6 laboratory mice cohoused with petstore. We hypothesized that cohousing would confer a basal transcriptional signature of immune activation to laboratory mice from petstore mice. Comparison of these data with existing human adult vs. neonatal PBMC expression profiling data (GSE27272) revealed close concordance of laboratory mice with human neonates, and of cohoused or petstore mice with human adults. Results highlight the impact of environment on the basal immune state and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modeling immunological events in free-living organisms, including humans. Total RNA was isolated from PBMC of C57Bl/6 laboratory mice, petstore mice and C57Bl/6 laboratory mice cohoused with petstore mice (at least after 60 days post-cohousing)and transcriptional comparison among 3 groups were performed.
2016-03-09 | E-GEOD-78979 | biostudies-arrayexpress
Project description:Laboratory mice comprise an inexpensive and expeditious model organism for preclinical vaccine testing; however, vaccine immunogenicity often fails to adequately translate to humans. Recent reports indicate that reconstituting physiologic microbial experience to specific pathogen free (SPF) mice induces durable immunological changes that better recapitulate the human immune system. We examined the impact of microbial experience on responses to vaccination after cohousing laboratory mice with pet store mice. We demonstrate that human transcriptional responses to influenza vaccination are better recapitulated in cohoused mice. Induction of humoral responses by vaccination was dampened in cohoused mice and resulted in poor control upon challenge. Additionally, the establishment of protective heterosubtypic T cell immunity was compromised in cohoused mice. In summary, SPF mice exaggerated both humoral and T cell protection induced by influenza vaccines compared to cohoused mice, suggesting that reconstituting microbial experience in laboratory mice through cohousing may better inform preclinical vaccine testing.
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Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as Crohn’s disease and colorectal cancer. Our data showed that Nod2-mediated risk of intestinal inflammation in colitis model is communicable to WT mice by cohousing. Here, we investigated if Nod2-deficient mice microbiota is able to change transcript profiles in Nod2-immunocompetent mice (C57Bl6/J mice) independently of colitis. Analysis used RNA extracted from colonic mucosa of C57Bl/6J mice co-housed with Nod2-deficient mice and C57Bl/6J mice alone. Direct comparisons of 4 biologicals replicates of C57Bl/6J mice cohoused with Nod2-deficient mice vs C57Bl/6J mice were performed.
2013-01-02 | E-GEOD-36481 | biostudies-arrayexpress
Project description:BACKGROUND: The transcript levels of many genes exhibit significant variation in tissue samples from inbred laboratory mice. A microarray experiment was designed to separate transcript abundance variation across samples from adipose, heart, kidney, and liver tissues of C57BL/6J mice into within-mouse and between-mouse components. Within-mouse variance captures variation due to heterogeneity of gene expression within tissues, RNA-extraction, and array processing. Between-mouse variance reflects differences in transcript levels between these genetically identical mice. Many biological sources can contribute to heterogeneous transcript levels within a tissue sample including inherent stochasticity of biochemical processes such as intrinsic and extrinsic noise within cells and differences in cell-type composition which can result from heterogeneity of stem and progenitor cell populations. Differences in global signaling patterns between individuals and micro-environmental influences such as interactions with pathogens and cage mates can also contribute to variation, but are likely to contribute more to the between-mouse variance component. RESULTS: The nature and extent of transcript abundance variation differs across tissues. Adipose has the largest total variance and the largest within-mouse variance. Liver has the smallest total variance, but it has the most between-mouse variation. Genes with high variability can be classified into groups with correlated patterns of expression that are enriched for specific biological functions. Variation between mice is associated with circadian rhythm, growth hormone signaling, immune response, androgen regulation, lipid metabolism, and the extracellular matrix. Genes showing correlated patterns of within mouse variation were also associated with biological functions, spatial connectivity of stochastic variation and heterogeneity of cell types within tissues. CONCLUSIONS: Genetically identical mice are individuals and they can experience different outcomes for medically important traits. This is reflected in the stochastic variation in gene expression observed between genetically identical mice. Much of the stochasticity has organismal, tissue, or spatial connectivity. Prior knowledge of the genes and functional classes of genes that are likely to vary in the absence of experimental perturbations, whether these are genetic or environmental, can inform experimental design decisions and the interpretation of gene expression data. Variation in gene expression in genetically identical mice sheds light on the impact of stochastic and micro-environmental factors and their phenotypic consequences.
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Project description:A 7-month inhalation study in C57BL/6 mice was conducted to evaluate long-term respiratory toxicity of e-vapor aerosols compared to cigarette smoke and to assess the impact of smoking cessation or switching to an e-vapor product after 3 months of exposure to 3R4F cigarette smoke (CS). In this study, we performed a chronic inhalation (4 h/day, 5 d/week, up to 7 months) study in C57BL/6 mice using a commercial (MarkTen®) e-vapor product and a combustible reference cigarette (3R4F) using a Switching and Cessation study design. A commercial e-vapor product (MarkTen® device [version 2.6.8]; “Test Red”) was supplied by Altria Client Services LLC (Richmond, VA, USA). The Test Red formulation was composed of aerosol formers (propylene glycol [PG] and vegetable glycerol [VG]), ~4% nicotine by weight, and flavors (non-menthol). The 3R4F commercial reference cigarettes were purchased from the University of Kentucky (Lexington, KY). HEPA filtered air at the testing facility (Battelle, West Jefferson, OH) was used as Sham Control. General procedures for animal care and housing met the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) recommendations and requirements stated in the “Guide for Care and Use of Laboratory Animals” [National Research Council (NRC)] and approved by the Institutional Animal Care and Use Committee (IACUC). Female C57BL/6 mice were received from Charles River Kingston (Stone Ridge, NY). Test atmosphere was generated from smoking machines and delivered to the mice through a nose-only exposure system. The modified Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) Reference Method 81 regimen (55/30/5: a 55 ± 0.3 mL puff volume, a puff every 30 seconds, a 5-second puff duration) was used to generate e-vapor aerosol for 130 puffs/cartridge. Mainstream smoke from 3R4F cigarette was generated using a modified Health Canada Intense regimen (55/30/2: a 55 ± 0.3 mL puff volume, a puff every 30 seconds, a 2-second puff duration, and a near-square puff profile) for 8 puffs/cigarette. Female C57BL/6 mice (~10 weeks old) were randomly assigned based on body weight to one of five exposure groups: Sham Control, 3R4F CS, Test Red, Switching, and Cessation. Mice were exposed to 3R4F CS (550 µg/L TPM) or e-vapor aerosols (Test Red; 1100 µg/L TPM) via nose-only inhalation up to 4 h/day, 5 d/week for up to 7 months. After the first 3 months of exposure, groups of 3R4F CS mice were subjected to exposures of: (1) Test Red aerosol (“Switching”) or (2) filtered air (“Cessation”), while a group of mice continued to be exposed to 3R4F CS. Here, the protein expression data for lung tissue assessed by iTRAQ®-based quantitative proteomics is reported.
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Project description:The relative contribution of genetic and environmental factors to variation in immune response is still poorly understood. Here, we performed a deep phenotypic analysis of immunological parameters and molecular profiles of laboratory mice released into an outdoor enclosure, carrying genetic susceptibility genes (Nod2 and Atg16l1) implicated in the development of inflammatory bowel diseases. Differences in lymphocyte populations were largely driven by the lab and wild environment. However, cytokine production after stimulation with microbial antigens showed a stronger genetic component in the lab, which was reduced after exposure to the wild environment. Multi-omic models identified key transcriptional factors associated with lymphocyte changes predictive of the environment, as well as sub-networks associated with cytokine responses against Candida albicans and Bacteroides vulgatus. Hence, exposing laboratory mice of different genetic backgrounds to the outdoor environment may identify important contributors to immune variation.
2019-12-01 | GSE135472 | GEO
Project description:The immune system of SPF mice is dominated by naïve phenotype immune cells, especially within the T cell compartment, and resembles that of neonatal humans (Beura et al., 2016; Reese et al., 2016). Sequential infection of SPF-housed laboratory mice with common experimental pathogens, such as MHV, MCMV, Listeria monocytogenes, LCMV, and influenza A virus (Berton et al., 2022; Reese et al., 2016), or cohousing (CoH) SPF mice with pet store mice carrying multiple pathogenic and commensal bacteria, viruses, and/or fungi (Beura et al., 2016) induces immune system alterations and maturations that more closely resemble the adult human immune system. Such microbial exposure drastically alters the composition and function of the immune system of laboratory mice, which can significantly influence the overall outcome (and survival) to subsequent infection. Here we report CD11b+ CD115+ monocytes sorted from female specific pathogen-free (SPF) C57BL/6N (B6) mice co-housed with petstore mice for 60 days are transcriptionally different than SPF CD11b+ CD115+ monocytes
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