Whole blood gene expression profiling at day 1, 3 and 7 after total-body irradiation in Gottingen minipigs
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ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE173427 | GEO | 2022/04/25
REPOSITORIES: GEO
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Project description:The present work identified gene expression changes in response to total body irradiation (TBI) in heart, lungs, and liver tissue in Gottingen minipigs. Animals were exposed to 1.7 Gy, 1.9 Gy, 2.1 Gy and 2.3 Gy of TBI and were followed for 45 days. Organ samples were collected at the end of 45 days or sooner if the animal displayed morbidity necessitating euthanasia. RNA was extracted and gene expression profiling studied using Agilent arrays.
2021-04-27 | GSE173425 | GEO
Project description:Description Primary membranous nephropathy (MN) is an autoimmune kidney disease histomorphologically defined by subepithelial deposition of immune complexes in the glomeruli, and exhibits a high risk for end-stage kidney disease. Circulating antibodies against phospholipase A2 receptor 1 (PLA2R1) are detected in 70-80% of MN patients and correlate with treatment response and prognosis. Experimental proof that human PLA2R1-antibodies induce MN is still missing. Methods: In passive transfer experiments, minipigs received plasma or purified IgG from patients with PLA2R1-associated MN or from healthy controls. PLA2R1-antibodies and proteinuria were monitored using Western blot, ELISA and Coomassie staining. Kidney tissues were analyzed using immunohistochemistry, immunofluorescence, electron microscopy and proteomic analyses. Results: We show that minipigs, like humans, express PLA2R1 on podocytes. Human PLA2R1-antibodies bound to minipig PLA2R1 in-vitro and in-vivo. Passive transfer of human PLA2R1-antibodies, derived from patients with PLA2R1- associated MN, led to the development of histomorphologic characteristics of human early-stage MN in minipigs, activation of components of the complement cascade and induction of low levels of proteinuria. In the later phases of disease, development of an autologous phase of disease was observed. Conclusions: Applying a translational approach from humans to minipigs we show that human PLA2R1-antibodies are pathogenic, although in the heterologous phase of disease only low level proteinuria developed. Proteomic samples: Porcine glomeruli were isolated following previously published protocols known for human glomeruli, with slight modifications (Stahl et al., Kidney Int. 1984;26(1):30–34.). A total of six samples of sieved glomeruli from porcine kidney were used. 1. untreated_negative_control Experiment 1 (passive transfer of human PLA2R1 antibody from PLA2R1-antibody positive patient into minipigs) 2. exp_1_passive_antibody_rep1 Same experimental procedure in two animals (replicate 1) (treated with patient antibody) 3. exp_1_passive_antibody_rep2 Same experimental procedure in two animals (replicate 2) (treated with patient antibody) 4. exp_1_passive_antibody_control control animal for Pig A and B (treated with healthy antibody) Experiment 2 (passive transfer of human plasma from PLA2R1-antibody positive patient into minipigs) 5. exp_2_passive_plasma treated animal (treated with patient plasma) 6. exp_2_passive_plasma_control control animal (treated with healthy plasma)
2022-12-21 | PXD039024 | Pride
Project description:Minipigs have favorable biological characteristics for juvenile toxicity studies to assess efficacy and safety of pediatric drug products. To evaluate at the molecular level the expression of drug targets, drug metabolism pathways or general maturation of organ transcriptomes in minipigs, we used Customized Agilent Micoarrays (Design-ID 050244) for genome-wide gene expression profiling on 9 different tissues from male and female juvenile Göttingen minipigs aged 1 week to 24 months. The gene expression results analyzed in this study are further described in Heckel T. et al. (2015) Functional analysis and transcriptional output of the Göttingen minipig genome. under submission
2015-12-16 | GSE71441 | GEO
Project description:Purpose: There is a need for point-of-care diagnostics for future mass casualty events involving radiation exposure. The development of radiation exposure and dose prediction algorithms for biodosimetry is needed for screening of large populations during these scenarios, and exploration of the potential effects which sex, age, genetic heterogeneity, and physiological comorbidities may have on the utility of biodosimetry diagnostics is needed. In the current study, proteomic profiling was used to examine sex specific differences in age matched C57BL6 mice on the blood proteome following radiation exposure and the usefulness of development and application of biodosimetry algorithms using both male and female samples. Methods: C57BL6 male and female mice between 9-11 weeks of age received a single total body radiation exposure of either 2, 4 or 8 Gy with plasma collection at days 1, 3 and 7 post-irradiation. Plasma was then screened using the SomaScan v4.1 assay for ~7000 protein analytes. A subset panel of protein biomarkers demonstrated significant (FDR<0.05 and |logFC|>0.2) changes in expression following radiation exposure. All proteins were used for feature selection to build predictive models of radiation exposure using different sample and sex specific cohorts. Both binary (prediction of any radiation exposure) and multidose (prediction of specific radiation dose) model series were developed using either female and male samples combined or only female or only male samples. The binary series (Models 1, 2 and 3) and multidose series (Models 4, 5 and 6) series included female/male combined, female only and male only respectively. Results: Detectable values were obtained for all ~7000 proteins included in the SomaScan assay for all samples. Each model algorithm built using a unique sample cohort was validated with a training set of samples and tested with a separate new sample series. Overall predictive accuracies in the binary model series was ~100% at the model training level and when tested with fresh samples 97.9% for Model 1(Female and Male) and 100% for Model 2 (Female only) and Model 3 (Male only). When sex specific Models’ 2 and 3 were tested with the opposite sex, the overall predictive accuracy rate dropped to 62.5% for Model 2 and remained 100% for Model 3. The overall predictive accuracy rate in the multidose model series was 100% for all models at the model training level and when tested with fresh samples 83.3%, 75% and 83.3% for Multidose Models 4-6 respectively. When sex specific Models’ 5 (Female only) and Model 6 (Male only) were tested with the opposite sex the overall predictive accuracy rate dropped to 52.1% and 68.8% respectively. Conclusion: These models represent novel predictive panels of radiation responsive proteomic biomarkers and illustrate the utility and necessity of considering sex specific differences in development of radiation biodosimetry prediction algorithms. As sex specific differences were observed in this study, and as use of point-of-care radiation diagnostics in future mass casualty settings will necessarily include persons of both sexes, consideration of sex specific variation is essential to ensure these diagnostic tools have practical utility in the field.
2024-05-11 | GSE267131 | GEO
Project description:Minipigs resemble many features of human anatomy, physiology, and biochemistry and represent an animal model for drug efficacy and safety testing. To evaluate at the molecular level the expression of drug targets, drug metabolism pathways or general features of organ transcriptomes in minipigs, we used Customized NimbleGen Microarrays (Design-ID: 120229_MiniPig_TH_expr_HX12) for genome-wide gene expression profiling on 18 different tissues from 6 male and 6 female Göttingen minipigs. The gene expression results analyzed in this study are further described in Heckel T. et al. (2015) Functional analysis and transcriptional output of the Göttingen minipig genome. under submission
2015-12-16 | GSE71438 | GEO
Project description:Minipigs have favorable biological characteristics for juvenile toxicity studies to assess efficacy and safety of pediatric drug products. To evaluate at the molecular level the expression of drug targets, drug metabolism pathways or general maturation of organ transcriptomes in minipigs, we used Customized Agilent Micoarrays (Design-ID 050244) for genome-wide gene expression profiling on 9 different tissues from male and female juvenile Göttingen minipigs aged 1 week to 24 months. The gene expression results analyzed in this study are further described in Heckel T. et al. (2015) Functional analysis and transcriptional output of the Göttingen minipig genome. under submission Data of 72 different tissue samples from 9 tissues (cerebral cortex, hypothalamus, cerebellum, liver, kidney, spleen, bone marrow, testis, ovary) and 4 age groups in female (1 week, 4 weeks, 2 months, 4 months) and 5 age groups in male (1 week, 4 weeks, 2 months, 4 months, 2 years) Goettingen minipigs (Ellegaard) were measured. One tissue was measured in 8 technical replicates. The combination of data of female and male pigs could be seen as a kind of biological replicate for most genes.
2015-12-16 | E-GEOD-71441 | biostudies-arrayexpress
Project description:Radiation-induced lung injury is a serious health threat to victims of radiological incidents or patients receive radiation in the thorax. Studying the gene expression in lung tissues after radiation exposure helps to understand the mechanism of radiation-induced lung injury.
2021-07-02 | GSE70943 | GEO
Project description:Understanding the possible impact of potential confounding factors is necessary for any approach to radiation biodosimetry. Potential confounding factors have not been fully addressed for gene expression-based biodosimetry approaches, such as we are developing. To begin addressing this need, we have used an ex vivo irradiated peripheral blood cell model to investigate the potential effect of smoking on the global radiation gene expression response, and looked for genes that respond to radiation differently in smokers and non-smokers, and also in males and females. The results indicate that only a small number of genes may be significantly confounded by either factor, supporting the idea of developing peripheral blood gene expression strategies for radiation biodosimetry.
2011-03-16 | GSE23515 | GEO
Project description:Minipigs resemble many features of human anatomy, physiology, and biochemistry and represent an animal model for drug efficacy and safety testing. To evaluate at the molecular level the expression of drug targets, drug metabolism pathways or general features of organ transcriptomes in minipigs, we used Customized NimbleGen Microarrays (Design-ID: 120229_MiniPig_TH_expr_HX12) for genome-wide gene expression profiling on 18 different tissues from 6 male and 6 female Göttingen minipigs. The gene expression results analyzed in this study are further described in Heckel T. et al. (2015) Functional analysis and transcriptional output of the Göttingen minipig genome. under submission A NimbleGen customized 12x135K Gene Expression Array [design ID: 120229_MiniPig_TH_expr_HX12] study using total RNA recovered from drug-naive minipig tissues. Each microarray measures the expression level of 24,499 probe sets covering 17,261 genes with five 60-mer probes (PM) per probe set. The number of replicates is 1 - i.e., only one set of probes on the array. The design includes 16,642 random GC probes for the estimation of the signal threshold and 1536 ERCC control probes.
2015-12-16 | E-GEOD-71438 | biostudies-arrayexpress
Project description:Understanding the possible impact of potential confounding factors is necessary for any approach to radiation biodosimetry. Potential confounding factors have not been fully addressed for gene expression-based biodosimetry approaches, such as we are developing. To begin addressing this need, we have used an ex vivo irradiated peripheral blood cell model to investigate the potential effect of smoking on the global radiation gene expression response, and looked for genes that respond to radiation differently in smokers and non-smokers, and also in males and females. The results indicate that only a small number of genes may be significantly confounded by either factor, supporting the idea of developing peripheral blood gene expression strategies for radiation biodosimetry. Blood from each of 24 different donors was exposed to four doses of ionizing radiation (0, 0.1, 0.5, or 2 Gy) and analyzed using single-color microarray hybridization. The donors represented equal numbers of male and female smokers (1 or more packs a day) and non-smokers. There are 95 data sets in the study as the sample from one of the female smokers exposed to 2 Gy was lost.
2011-03-16 | E-GEOD-23515 | biostudies-arrayexpress