Type I interferons were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of interferon antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of interferon-induced antiviral activity. Here we identify a novel role for RNase-L in the host antibacterial response. RNase-L-/- mice exhibited a dramatic increase in mortality following
An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity.
No sample metadata fields
View SamplesHomozygous disruption of c-Maf led to embryonic lethality and impaired erythroblastic island formation. c-Maf is expressed in the fetal liver macrophages. It suggests that macrophages are responsible for the lethality of c-Maf knock-out embryos. To search downstream genes of c-Maf, we surveyed genes associated with macrophage function by microarray analysis.
c-Maf plays a crucial role for the definitive erythropoiesis that accompanies erythroblastic island formation in the fetal liver.
Specimen part
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Bifidobacteria can protect from enteropathogenic infection through production of acetate.
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View SamplesBackground: The ErbB3 binding protein-1 (Ebp1) belongs to a family of DNA/RNA binding proteins implicated in cell growth, apoptosis and differentiation. However, the physiological role of Ebp1 in the whole organism is not known. Therefore, we generated Ebp1-deficient mice carrying a gene trap insertion in intron 2 of the Ebp1 (pa2g4) gene.
Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1) deficient mice.
No sample metadata fields
View SamplesProductive rearrangement of the immunoglobulin heavy chain locus triggers a major developmental checkpoint that promotes limited clonal expansion of pre-B cells, culminating in cell cycle arrest and rearrangement of the kappa () or lambda () light-chain loci. B lineage cells lacking the related transcription factors IRF-4 and IRF-8 undergo a developmental arrest at the cycling pre-B cell stage and are blocked for light-chain recombination. Using Irf-4,8-/- pre-B cells we demonstrate that two pathways converge to synergistically drive light-chain rearrangement, a process that is not simply activated by cell cycle exit. One pathway is directly dependent on IRF-4, whose expression is elevated by pre-BCR signaling. IRF-4 targets the 3 and enhancers to increase locus accessibility and positions a kappa allele away from pericentromeric heterochromatin. The other pathway is triggered by attenuation of IL-7 signaling and results in activation of the intronic enhancer via binding of the transcription factor, E2A. Intriguingly, IRF-4 regulates the expression of CXCR4 and promotes the migration of pre-B cells in response to the chemokine CXCL12. We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7 expressing stromal cells.
Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling.
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View SamplesGoal of experiment: Identify genes down-regulated between pre- and post-natal stages in mouse dental papillae.
Down-regulated genes in mouse dental papillae and pulp.
No sample metadata fields
View SamplesThe objective of this study was to identify alterations in gene expression during reverse myocardial remodeling in a mouse model of reversible pressure overload.
Collagen isoform shift during the early phase of reverse left ventricular remodelling after relief of pressure overload.
No sample metadata fields
View SamplesBALB/c mice are susceptible to proteoglycan (PG) aggrecan-induced arthritis (PGIA), and the absence of TSG-6 further increases susceptibility and local inflammatory reactions, including neutrophil invasion into the joints. To gain insight into the mechanisms of TSG-6 action, synovial fibroblasts were isolated from wild-type and TSG-6-KO mice, cultured and exposed to various agents affecting either the TSG-6 expression and/or modify the intracellular function of TSG-6.
TSG-6 protein, a negative regulator of inflammatory arthritis, forms a ternary complex with murine mast cell tryptases and heparin.
Sex, Treatment
View SamplesIre1 conditional null or control mice of 3-months old were injected intraperitoneally with TM or vehicle.
The unfolded protein response transducer IRE1α prevents ER stress-induced hepatic steatosis.
Specimen part
View SamplesIt is widely believed that the carcinogenic action of ionizing radiation is due to targeted DNA damage and resulting mutations, but there is also substantial evidence that non-targeted radiation effects alter epithelial phenotype and the stromal microenvironment. Activation of transforming growth factor 1 (TGF) is a non-targeted radiation effect that mediates cell fate decisions following DNA damage and regulates microenvironment composition; it could either suppress or promote cancer. We asked if such non-targeted radiation effects contribute to carcinogenesis by using a novel radiation chimera model. Unirradiated Trp53 null mammary epithelium was transplanted to the mammary stroma, previously divested of endogenous epithelia, of mice previously exposed to a single low (10 -100 cGy) radiation dose. By 300 days, 100% of transplants in irradiated hosts at either 10 or 100 cGy had developed Trp53 null breast carcinomas compared to 54% in unirradiated hosts. Tumor growth rate was also increased by high, but not low, dose host irradiation. In contrast, irradiation of Tgfb1 heterozygote mice prior to transplantation failed to decrease tumor latency, or increase growth rate at any dose. Host irradiation significantly reduced the latency of invasive ductal carcinoma compared to spindle cell carcinoma. However, irradiation of either host genotype significantly increased the frequency of estrogen receptor negative tumors. These data demonstrate two concepts critical to understanding radiation risks. First, non-targeted radiation effects can significantly promote the frequency and alter the features of epithelial cancer. Second, radiation-induced TGF activity is a key mechanism of tumor promotion.
Radiation acts on the microenvironment to affect breast carcinogenesis by distinct mechanisms that decrease cancer latency and affect tumor type.
Age, Specimen part
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