To identify gene(s) that are modified in their relative expression levels in the Potocki-Lupski Syndrome mouse model and map to the rearranged region, i.e. possible candidate genes at the source of the PTLS-like phenotypes shown by the PTLS mouse, we comp
Abnormal social behaviors and altered gene expression rates in a mouse model for Potocki-Lupski syndrome.
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View SamplesCystic 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.
Intestinal phenotype of variable-weight cystic fibrosis knockout mice.
Sex
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Vitamin C supplementation modulates gene expression in peripheral blood mononuclear cells specifically upon an inflammatory stimulus: a pilot study in healthy subjects.
Specimen part
View SamplesThe epigenetic changes of the chromatin represent an attractive molecular substrate for adaptation to the environment. We examined here the role of CBP, a histone acetyltransferase involved in mental retardation, in the genesis and maintenance of long-lasting systemic and behavioral adaptations to environmental enrichment (EE). Morphological and behavioral analyses demonstrated that EE ameliorates deficits associated to CBP-deficiency. However, CBP-deficient mice also showed a strong defect in environment-induced neurogenesis and impaired EE-enhanced spatial navigation and patter separation ability. These defects correlated with an attenuation of the transcriptional program induced in response to EE and with deficits in histone acetylation at the promoters of EE-regulated, neurogenesis-related genes. Additional experiments in CBP restricted and inducible knockout mice indicated that environment-induced adult neurogenesis is extrinsically regulated by CBP function in mature granule cells. Overall, our experiments demonstrate that the environment alters gene expression by impinging on activities involved in modifying the epigenome and identify CBP-dependent transcriptional neuroadaptation as an important mediator of EE-induced benefits, a finding with important implications for mental retardation therapeutics.
CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement.
Sex, Age, Specimen part
View SamplesA role of vitamin C (ascorbic acid) as an antioxidant molecule has been recognized, largely based on in vitro studies. However, more recently, the concept of antioxidant molecule has been reconsidered and its biological function is no longer considered to be simply due to its ability to act as electron donors, rather, it appears to act by modulating signaling and gene expression.
Vitamin C supplementation modulates gene expression in peripheral blood mononuclear cells specifically upon an inflammatory stimulus: a pilot study in healthy subjects.
Specimen part
View SamplesMetastasis is the leading cause of death for cancer patients. Consequently it is imperative that we improve our understanding of the molecular mechanisms that underlie progression of tumour growth towards malignancy. Advances in genome characterisation technologies have been very successful in identifying commonly mutated or misregulated genes in a variety of human cancers. However the difficulty in evaluating whether these candidate genes drive tumour progression remains a major challenge. Using the genetic amenability of Drosophila melanogaster we generated tumours with specific genotypes in the living animal and carried out a detailed systematic loss-of-function analysis to identify conserved genes that enhance or suppress epithelial tumour progression. This enabled the discovery of functional cooperative regulators of invasion and the establishment of a network of conserved invasion suppressors. This includes constituents of the cohesin complex, which can either promote individual or collective invasion, depending on the severity of effect on cohesin function.
A Genetic Analysis of Tumor Progression in Drosophila Identifies the Cohesin Complex as a Suppressor of Individual and Collective Cell Invasion.
Cell line
View SamplesCystatin D (CST5) is an inhibitor of several proteases of the cathepsin family that inhibits cell proliferation, migration and invasion of colon carcinoma cells. Some of these effects are unrelated to its antiprotease activity. Here, we use genome-wide expression microarrays to show that cystatin D regulates gene expression (including that of genes encoding transcription factors such as RUNX1, RUNX2, or MEF2C) in HCT116 cells.
Cystatin D locates in the nucleus at sites of active transcription and modulates gene and protein expression.
Specimen part, Cell line
View SamplesParthenogenetic stem cells were derived from parthenotes, then differentiated to mesenchymal stem cells. These were further reprogrammed to induced pluripotent stem cells, which were finally differentiated to secondary mesenchymal stem cells.
Accumulation of instability in serial differentiation and reprogramming of parthenogenetic human cells.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.
Sex, Specimen part, Disease, Disease stage, Subject
View SamplesWe analysed the RNA profile of IPSC-derived dopaminergic neurons from idiophatic and genetic form (LRRK2) of Parkinsons disease (PD). Both, idiopathic and genetic form of the disease show similar expression alterations and were merged in one whole PD group. We found 437 differentially expressed genes (DEGs) in the PD group as a whole. Up-regulated DEGs (n=254) encompassed genes involved in neural functions and transcription factor functions whereas down-regulated DEGs (n=183) affected basic homeostasis. These data point towards the presence of gene - and also protein - expression changes in DAn from PD patients which co-occur simultaneously along with DNA methylation changes.
Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.
Sex, Specimen part, Disease, Disease stage
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