Light-controlled in situ synthesis of DNA microarrays (Affymetrix GeneChip Mouse Genome 430 2.0) were performed to determine the altered gene expression. Affymetrix algorithm and multiple analysis comparison software were used for assessing gene expression differences, and mRNAs that increased or decreased in the brains of NP(-M)-treated mice relative to that in the brains of Blank-NP-treated mice were identified.
No associated publication
Sex, Age, Specimen part
View SamplesWe found miR-125a was a key regulator that stabilizes the commitment and immunoregulatory capacity of Treg cells.To gain insights into the general functional features of miR-125a-deficient Treg cells, we performed a genome-wide gene array analysis on Treg population isolated from the spleens of 6 to 8-week-old miR-125a-deficient and WT mice
No associated publication
Specimen part
View SamplesBisphenol A (BPA), an endocrine-disrupting chemical (EDC), is a well-known, ubiquitous estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we first examined the alterations of in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS).
Endocrine disrupter bisphenol A increases in situ estrogen production in the mouse urogenital sinus.
Specimen part
View SamplesThe serine threonine kinase Stk40 has been shown to involve in mouse embryonic stem cell differentiation, pulmonary maturation and adipocyte differentiation. Here we report that targeted deletion of Stk40 leads to fetal liver hypoplasia and anemia in the mouse embryos. The reduction of erythrocytes in the fetal liver is accompanied by increased apoptosis and compromised erythroid maturation. Stk40-/- fetal liver cells have significantly reduced colony forming units (CFUs) capable of erythroid differentiation, including burst forming unit-erythroid (BFU-E), colony forming unit-erythroid (CFU-E), and CFU-granulocyte, erythrocyte, megakaryocyte and macrophage (CFU-GEMM), but not CFU-granulocyte/macrophages (CFU-GM). Purified Stk40-/- megakaryocyte-erythrocyte progenitors (MEPs) produced substantially fewer CFU-E colonies compared to control cells. Moreover, Stk40-/- fetal liver erythroblasts failed to form normal erythroblastic islands in association with wild type or Stk40-/- macrophages, indicating an intrinsic defect of Stk40-/- erythroblasts. Furthermore, the hematopoietic stem and progenitor cell pool is reduced in Stk40-/- fetal livers but still retains the multi-lineage reconstitution capacity. Finally, analysis of microarray data of E14.5 fetal liver cells suggests a potential role of aberrantly activated TNF- signaling in Stk40 depletion induced dyserythropoiesis with a concomitant increase in cleaved Caspase-3 and decrease in Gata1 proteins. Altogether, the identification of Stk40 as a regulator for fetal erythroid differentiation, maturation and survival provides new clues to the molecular regulation of erythropoiesis and related diseases.
No associated publication
Specimen part
View SamplesThe -amyloid precursor protein APP and the related APLPs, undergo complex proteolytic processing giving rise to several fragments. Whereas it is well established that A accumulation is a central trigger for Alzheimer disease (AD), the physiological role of APP family members and their diverse proteolytic products is still largely unknown. The secreted APPs ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The -secretase generated APP intracellular domain AICD, functions as a transciptional regulator in heterologous reporter assays, although its role for endogenous gene regulation has remained controversial. To gain further insight into the molecular changes associated with knockout phenotypes and to elucidate the physiological functions of APP family members including their proposed role as transcriptional regulators we performed a DNA microarray transcriptome profiling of the frontal cortex of adult wild type, APP-/-, APLP2-/- and APPs knockin (KI) mice, APP/, expressing solely the secreted APPs ectodomain. Biological pathways affected by the lack of APP family members included regulation of neurogenesis, regulation of transcription and regulation of neuron projection development. Comparative analysis of transcriptome changes and qPCR validation identified co-regulated gene sets. Interestingly, these included heat shock proteins and plasticity related genes that were down-regulated in knock-out cortices. In contrast, we failed to detect significant differences in expression of previously proposed AICD target genes including Bace1, Kai1, Gsk3b, p53, Tip60 and Vglut2. Only Egfr was slightly up-regulated in APLP2-/- mice. Comparison of APP-/- and APP/ with wild-type mice revealed a high proportion of co-regulated genes indicating an important role of the C-terminus for cellular signaling. Finally, comparison of APLP2-/- on different genetic backgrounds revealed that background related transcriptome changes may dominate over changes due to the knockout of a single gene. Shared transcriptome profiles corroborated closely related physiological functions of APP family members in the adult central nervous system. As expression of proposed AICD target genes was not altered in adult cortex, this may indicate that these genes are not affected by lack of APP under resting conditions or only in a small subset of cells.
Comparative transcriptome profiling of amyloid precursor protein family members in the adult cortex.
Sex, Specimen part
View SamplesDespite its key role in Alzheimer pathogenesis, the physiological function(s) of the amyloid precursor protein (APP) and of its proteolytic fragments are still poorly understood. The secreted APPs ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The -secretase generated APP intracellular domain, AICD, functions as a transcriptional regulator in heterologous reporter assays although its role for endogenous gene regulation has remained controversial. Previously, we have generated APPs knockin (KI) mice expressing solely the secreted ectodomain APPs. Here, we generated double mutants (APPs-DM) by crossing APPs-KI mice onto an APLP2-deficient background and show that APPs rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice. Despite normal CNS morphology and unaltered basal synaptic transmission, young APPs-DM mice already showed pronounced hippocampal dysfunction, impaired spatial learning and a deficit in LTP. To gain further mechanistic insight into which domains/proteolytic fragments are crucial for hippocampal APP/APLP2 mediated functions, we performed a DNA microarray transcriptome profiling of prefrontal cortex and hippocampus of adult APLP2-KO (APLP2-/-) and APPs-DM mice (APP/APLP2-/- mice).Interestingly, this analysis failed to reveal major genotype-related transcriptional differences. Expression differences between cortex and hippocampus were, however, readily detectable.
APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP.
Sex, Specimen part
View SamplesWe performed RNA-sequencing on four groups of zebrafish larvae: control, Tg(Myc), Tg(Kras), Tg(Myc)&Tg(Kras) to analyze the expression of genes involved in the lipid-associated pathways.The results revealed high dynamic alterations in almost all aspects of lipid metabolism, among which, the expressions of genes involved in TG/DG/GP transformation and FA desaturation/elongation displayed intensive changes, in consistent with our observations in lipodomics profiling
No associated publication
None
No sample metadata fields
View SamplesGene expression microarrays were performed to investigate the molecular effects of exposure to environmental polluted groundwater. Zebrafish was treated with polluted waters collected from dumps located upstream and downstream a sanitary landfills. Gene expression profiling of zebrafish liver was analyzed after acute exposure to sampled waters.
Cross-species toxicogenomic analyses and phenotypic anchoring in response to groundwater low-level pollution.
None
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Specimen part
View SamplesCerebellar post-natal development is particularly sensitive to thyroid hormone and low levels of thyroid hormone (hypothyroidism) result in permanent defects in cerebellar architecture and function. All cell types of the cerebellum are affected, but the main sign of hypothyroidism in mice is the persistence of the external granular layer, composed of mitotic neuronal precursors at P21.
No associated publication
Specimen part
View Samples