Equine herpesvirus 1 (EHV-1) is the causative agent of a number of equine pathological states, including severe disease of the central nervous system, respiratory infections, and abortion storms. Our results showed that intranasal immunization with CpG-B oligodeoxynucleotides (ODN) protects CBA mice from lethal EHV-1 challenge. IFN-γ and seven interferon-stimulated genes (ISGs) were upregulated 39.4- to 260.3-fold at 8 h postchallenge in the lungs of RacL11-challenged mice that had been immunized with CpG-B ODN. Treatment with 20 ng/ml of IFN-γ reduced EHV-1 yield by 100-fold in MH-S at 4 days post-VZV infection compared to that of untreated cells. However, IFN-γ reduced virus yield by only 2-fold in and mouse fibroblast L-M cells. To identify IFN-γ-stimulated genes that inhibit EHV-1 replication, Affymetrix microarray analyses were performed with IFN-γ-treated MH-S and L-M cells. In MH-S cells, IFN-γ upregulated 551 genes and down-regulated 136 genes as compared to those of untreated cells. In L-M cells, IFN-γ upregulated 225 genes and downregulated 2 genes. Nine genes associated with innate immune response were significantly upregulated only in MH-S cells. Five antiviral ISGs MX1, SAMHD1, NAMPT, TREX1, and DDX60 were upregulated 3.2- to 18.1-fold only in MH-S cells. These results suggest that CpG-B ODN may be used as a prophylactic agent in horses.
Interferon Gamma Inhibits Equine Herpesvirus 1 Replication in a Cell Line-Dependent Manner.
Specimen part, Cell line, Treatment
View SamplesThe overall goal of this project is to investigate the role of TGF-beta signaling in tissue-tissue interactions between myogenic precursors of craniofacial muscles and cranial neural crest cells (CNCCs). Here, we conducted gene expression profiling of the tongue bud from mice at embryonic day E13.5 with a CNCC-specific conditional inactivation of the TGF-beta receptor type 1 gene Alk5. These mice provide a model of microglossia as well as disrupted extraocular and masticatory muscle development, which are congenital birth defects commonly observed in several syndromic conditions.
ALK5-mediated transforming growth factor β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions.
Sex, Specimen part
View SamplesThe overall goal of this project is to investigate the role of TGF-beta signaling in tissue-tissue interactions between myogenic precursors of craniofacial muscles and cranial neural crest cells (CNCCs). Here, we conducted gene expression profiling of the mandibular arch from mice at embryonic day E11.5 with a CNCC-specific conditional inactivation of the TGF-beta receptor type 1 gene Alk5. These mice provide a model of microglossia as well as disrupted extraocular and masticatory muscle development, which are congenital birth defects commonly observed in several syndromic conditions.
ALK5-mediated transforming growth factor β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions.
Sex, Specimen part
View SamplesIsoniazid induced varying degrees of hepatic steatosis in an inbred strain Mouse Diversity Panel (MDP) study. RNA was isolated from all animals for analysis of gene expression changes in the liver. The objective of this study was to identify gene expression changes that drive isoniazid-induced steatosis.
A systems biology approach utilizing a mouse diversity panel identifies genetic differences influencing isoniazid-induced microvesicular steatosis.
Sex, Specimen part, Treatment
View SamplesThe process for evaluating chemical safety is inefficient, costly, and animal intensive. There is growing consensus that the current process of safety testing needs to be significantly altered to improve efficiency and reduce the number of untested chemicals. In this study, the use of short-term gene expression profiles was evaluated for predicting the increased incidence of mouse lung tumors. Animals were exposed to a total of 26 diverse chemicals with matched vehicle controls over a period of three years. Upon completion, significant batch-related effects were observed. Adjustment for batch effects significantly improved the ability to predict increased lung tumor incidence. For the best statistical model, the estimated predictive accuracy under honest five-fold cross-validation was 79.3% with a sensitivity and specificity of 71.4 and 86.3%, respectively. A learning curve analysis demonstrated that gains in model performance reached a plateau at 25 chemicals, indicating that the size of the current data set was sufficient to provide a robust classifier. The classification results showed a small subset of chemicals contributed disproportionately to the misclassification rate. For these chemicals, the misclassification was more closely associated with genotoxicity status than efficacy in the original bioassay. Statistical models were also used to predict dose-response increases in tumor incidence for methylene chloride and naphthalene. The average posterior probabilities for the top models matched the results from the bioassay for methylene chloride. For naphthalene, the average posterior probabilities for the top models over-predicted the tumor response, but the variability in predictions were significantly higher. The study provides both a set of gene expression biomarkers for predicting chemically-induced mouse lung tumors as well as a broad assessment of important experimental and analysis criteria for developing microarray-based predictors of safety-related endpoints.
Use of short-term transcriptional profiles to assess the long-term cancer-related safety of environmental and industrial chemicals.
Sex, Age, Specimen part, Disease, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
Sex, Age, Specimen part, Treatment
View SamplesThe role of Gata2 in regulating uterine function including fertility, implantation, decidualization and P4 signaling in the mouse was investigated by the conditional ablation of Gata2 in the uterus using the (PR-cre) mouse and ChIP-seq for in vivo GATA2 binding sites in the murine uterus upon acute P4 administration.
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
Sex, Age, Specimen part
View SamplesLung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1s expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer.
ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.
Age, Specimen part
View SamplesAfter positive selection in the thymus, the newly generated single positive (SP) thymocytes are phenotypically and functionally immature and undergo apoptosis upon antigen stimulation. In the thymic medullary microenvironment, SP cells progressively acquire immunocompetence. Negative selection to remove autoreactive T cells also occur at this stage. We have defined four subsets of CD4 SP, namely, SP1, SP2, SP3, and SP4 that follow a functional maturation program and a sequential emergence during mouse ontogeny.
The molecular signature underlying the thymic migration and maturation of TCRαβ+ CD4+ CD8 thymocytes.
Specimen part
View SamplesThere is evidence for the beneficial effect of FK506, an effective immunosuppressive agent, for the treatment of asthma however, the mechanisms underlying these effects are unclear. Using a mouse model of airway inflammation induced by Papain, a protease allergen, and RNAseq analysis of lung innate cells, we found that FK506 inhibited the activation of ILC2s, which initiate airway inflammation, as well as the induction of TH2 cells, which cause chronic inflammation. Our findings further support the clinical value of FK506 for the treatment of allergen-induced airway inflammation and clarify its targets and mechanisms of action. Overall design: Lung ILC2 cells, epithlial cells (type 1: AEC1 and type 2: AEC2), and basophils of mice were sorted and analyzed the transcriptome using Illumina HiSeq1500.
No associated publication
Age, Specimen part, Genotype, Treatment, Subject
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