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GSE5715
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cystic fibrosis transmembrane conductance regulator (Cftr) knockout mice present the clinical features of low body weight and intestinal disease permitting an assessment of the interrelatedness of these phenotypes in a controlled environment. To identify intestinal alterations which affect body weight in CF mice the histological phenotypes of crypt-villus axis height, goblet cell hyperplasia, and mast cell infiltrate were measured, cardiac blood samples assessed, and gene expression profiling of the ileum was completed for 12 week old (C57BL/6xBALB) F2 Cftrtm1UNC and non-CF mice presenting a range of body weight. Crypt-villus axis height decreased with increasing weight in CF, but not control, mice. Goblet cell hyperplasia and mast cell infiltration in the submucosa and muscularis externa layers of the CF intestine, were identified to be independent of bodyweight. Blood triglyceride levels were found to be significantly lower in CF mice than control mice (p = 3.02 x 10-5) but were not dependent on CF mouse body weight. By expression profiling, genes of DNA replication and lipid metabolism were among those altered in CF mice relative to non-CF controls; and no differences in gene expression were measured between samples from CF mice in the 25th and 75th percentile for weight. This study indicates that the absence of Cftr leads to altered morphology in the CF intestine the extent of which is correlated with body weight in CF mice while CF related changes in blood triglyceride levels and in the intestinal gene expression profile were not dependent on body weight in this model.
Publication Title
Intestinal phenotype of variable-weight cystic fibrosis knockout mice.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
ATP6AP2 is an essential accessory component of the vacuolar H+ ATPase (V-ATPase) and has been associated with intellectual disabilities (ID) and Parkinsonism. ATP6AP2 has been implicated in several signaling pathways, but little is known about its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional ATP6AP2 Drosophila and mouse models in the nervous system. In Drosophila, knockdown of ATP6AP2 induced defective phototaxis and vacuolisation of photoreceptor neurons and pigment cells when deleted in eyes and alteration of short- and long-term memory when deleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2Camk2aCre/0 mice) caused increased spontaneous locomotor activity and altered memory for fear. Both Drosophila ATP6AP2 knockdown and Atp6ap2Camk2aCre/0 mice presented with presynaptic transmission defect, abnormal number and morphology of synapses, and alteration of axonal transport in fly. In addition, Atp6ap2Camk2aCre/0 mice showed autophagy defect leading to axonal and neuronal degeneration in the cortex and the hippocampus. Surprisingly, myelinisation of axons was affected in our mutant mice. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2Camk2aCre/0 mouse hippocampi revealed dysregulated genes involved in myelination, action potential, membrane bound vesicles and adult behaviour. In summary, disruption of ATP6AP2 in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. Overall design: 4 samples, 2 wt and 2 Atp6ap2Camk2aCre/0
Publication Title
Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 19 Downloadable Samples
- Affymetrix HT MG-430 PM Array Plate (htmg430pm), Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Macrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.
Publication Title
Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm), Affymetrix HT MG-430 PM Array Plate (htmg430pm)
Description
Macrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.. The data cast further doubt upon the predictive value of mouse models of inflammatory disease.
Publication Title
Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The specialisation of mammalian cells in time and space requires genes associated with specific pathways and functions to be co-ordinately expressed. Here we have combined a large number of publically available microarray datasets (745 samples, from over 100 separate studies) derived from human primary cells and analysed on the Affymetrix U133plus2.0 array. Using the network analysis tool BioLayout Express3D we have constructed and clustered large correlation graphs of these data in order to identify robust co-associations of genes expressed in a wide variety of cell lineages. We discuss the biological significance of a number of these associations, in particular the coexpression of key transcription factors with the genes that they are likely to control. We consider the regulation of genes in human primary cells and specifically in the human mononuclear phagocyte system. Of particular note is the fact that these data do not support the identity of putative markers of antigen-presenting dendritic cells, nor classification of M1 and M2 activation states, a current subject of debate within immunological field. We have provided this data resource on the BioGPS web site (www.biogps.org) and on macrophages.com (www.macrophages.com).
Publication Title
An expression atlas of human primary cells: inference of gene function from coexpression networks.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 64 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The activation profiles of macrophages under different immune and inflammatory conditions have generated great interest. LPS, in particular, is a commonly used in vitro model of infection and inflammation studies in macrophages. We have used gene expression microarrays to define the effects of each of three variables; LPS dose, LPS vs. interferons beta and gamma, and genetic background on the transcriptional response of mouse bone marrow-derived macrophages
Publication Title
Analysis of the transcriptional networks underpinning the activation of murine macrophages by inflammatory mediators.
Sample Metadata Fields
No sample metadata fields
View Samples- Equus caballus
- 13 Downloadable Samples
- Equus caballus Gene 1.0 ST Array (equgene10st)
Description
Alveolar macrophages are the first line of defense against pathogens in the lungs of all mammalian species and therefore may constitute an appropriate therapeutic target cell in the treatment and prevention of opportunistic airway infections. Analysis of alveolar macrophages from several species has revealed a unique cellular phenotype and transcriptome, presumably linked to their distinct airway environment and function in host defense. The current study extends these findings to the horse.
Publication Title
Comparative transcriptome analysis of equine alveolar macrophages.
Sample Metadata Fields
Treatment
View Samples- Mus musculus, Homo sapiens
- 86 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st), Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Assembly of a Parts List of the Human Mitotic Cell Cycle Machinery.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Transcriptional programmes involved in the eukaryotic cell cycle are activated sequentially throughout the process. In particular, the set of genes required for S and G2-M phases are highly conserved and induced one after the other.
Publication Title
Assembly of a Parts List of the Human Mitotic Cell Cycle Machinery.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 22 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Mouse bone marrow-derived macrophages (BMDM) grown in macrophage colony-stimulating factor (CSF-1) have been used widely in studies of macrophage biology and the response to toll-like receptor agonists. We investigated whether similar cells could be derived from the domestic pig. Cultivation of pig bone marrow cells for 5-7 days in presence of rhCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, CD163, CD172a), are potent phagocytic cells and produced tumor necrosis factor (TNF) in response to lipopolysaccharide (LPS). Bone marrow cells could be stored frozen and thawed, providing a renewable resource.
Publication Title
Pig bone marrow-derived macrophages resemble human macrophages in their response to bacterial lipopolysaccharide.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples