The ectopic expression of a Col10a1-13del transgene in osteocytes induced ER stress, compromising their differentiation and expression of Sclerostin, resulting in generalized bone overgrowth resembling human crainodiaphyseal chondrodysplasia (CCD).
Activating the unfolded protein response in osteocytes causes hyperostosis consistent with craniodiaphyseal dysplasia.
Specimen part
View SamplesNeutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis of S. aureus-infected skin revealed that induction of neutrophil recruitment genes was largely dependent upon IL-1beta/IL-1R activation. Unexpectedly, using IL 1beta reporter mice, neutrophils were identified as the primary source of IL-1beta at the site of infection. Furthermore, IL-1beta-producing neutrophils were necessary and sufficient for abscess formation and bacterial clearance. S. aureus-induced IL 1beta production by neutrophils required TLR2, NOD2, FPRs and the ASC/NLRP3 inflammasome. Taken together, IL-1beta and neutrophil abscess formation during an infection are functionally, spatially and temporally linked as a consequence of direct IL-1beta production by neutrophils.
Neutrophil-derived IL-1β is sufficient for abscess formation in immunity against Staphylococcus aureus in mice.
Specimen part
View SamplesMEG3 (Maternally Expressed Gene 3) is a non-coding RNA that is highly expressed in the normal human brain and pituitary. Expression of MEG3 is lost in gonadotroph-derived clinically non-functioning pituitary adenomas. Meg3 knock-out mice were generated to identify targets and potential functions of this gene in embryonic development and tumorigenesis. Gene expression profiles were compared in the brains of Meg3-null embryos and wild-type litter-mate controls using microarray analysis. Microarray data were analyzed with GeneSifter which uses Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) classifications to identify signaling cascades and functional categories of interest within the data set. Differences were found in signaling pathways and ontologies related to angiogenesis between wild-type and knock-out embryos. Quantitative RT-PCR and histological staining showed increased expression of some VEGF pathway genes and increased cortical microvessel density in the knock-out embryos. These results are consistent with reported increases in VEGF signaling observed in human clinically non-functioning pituitary adenomas. In conclusion, Meg3 may play an important role in control of vascularization in the brain and may function as a tumor suppressor by preventing angiogenesis.
Increased expression of angiogenic genes in the brains of mouse meg3-null embryos.
Specimen part
View SamplesTERT is an essential protein component of telomerase, a ribonuclearprotein complex that protects chromosomal ends. Ectopic expression of TERT in mouse skin activates hair follicle stem cells and induces active growth phase of hair cycles, called anagen. This activity of TERT is independent of its reverse transcriptase function, indicating that this is a non-telomeric function of TERT.
TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program.
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Phf8 histone demethylase deficiency causes cognitive impairments through the mTOR pathway.
Age, Specimen part
View SamplesWe used microarrays to detail the global programme gene expression of Phf8 knock out and wild type mice
Phf8 histone demethylase deficiency causes cognitive impairments through the mTOR pathway.
Age, Specimen part
View SamplesKeratinocytes are the major constituent of epithelial cells at mucosal surfaces and skin, which cover organs, internal cavities and the body. Traditionally, keratinocytes have been considered as an inert component of the multilayered epithelium to protect the subepithelial compartments from the pathogenic microorganisms, toxic stimuli and physical trauma. However, accumulated researches of the airway, gastrointestinal tract and skin have demonstrated that keratinocytes function in the development of the immune system, promotion of pathologic inflammation and even impose diverse decisions on immune cells.
Genome-wide analysis reveals the active roles of keratinocytes in oral mucosal adaptive immune response.
Specimen part, Time
View SamplesPolycomb group (PcG) proteins are epigenetic silencers whose dysregulation is frequently linked to cancer via mechanisms that remain unclear. Using conditional knock-out mice in a colitis-associated colorectal cancer (CAC) model, we found that Bmi1 and Mel18 are important initiation and maintenance factors during CAC tumorigenesis. Epithelial depletion of both Bmi1 and Mel18, but not either gene alone, significantly reduces tumor growth and multiplicity.
BMI1 and MEL18 Promote Colitis-Associated Cancer in Mice via REG3B and STAT3.
Specimen part
View SamplesThe gastrointestinal (GI) tract can have significant impact on the regulation of the whole body metabolism and may contribute to the development of obesity and diabetes. To systemically elucidate the role of the GI tract in obesity, we performed a transcriptomic analyses in different parts of the GI tract of two obese mouse models: ob/ob and high-fat diet (HFD) fed mice. Compared to their lean controls, both obese mouse groups had significant amount of gene expression changes in the stomach (ob/ob: 959; HFD: 542), much more than the number of changes in the intestine. Despite the difference in genetic background, the two mouse models shared 296 similar gene expression changes in the stomach. Among those genes, some had known associations to obesity, diabetes and insulin resistance. In addition, the gene expression profile strongly suggested an increased gastric acid secretion in both obese mouse models, probably through an activation of the gastrin pathway. In conclusion, our data reveal a previously unknown dominant connection between the stomach and obesity.
Significant obesity-associated gene expression changes occur in the stomach but not intestines in obese mice.
Specimen part
View SamplesThe goal of this experiment was to investigate the early mechanisms of human fulminant hepatitis through ConA-induced hepatitis model.Early diagnosis and interventions are important for patients with fulminant hepatitis and gene expression may be pivotal in the early diagnosis.
Genes related to the very early stage of ConA-induced fulminant hepatitis: a gene-chip-based study in a mouse model.
Sex, Specimen part, Time
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