AIRmax and AIRmin mouse lines show a differential lung inflammatory response and differential lung tumor susceptibility after urethane treatment, thus constituting a good genetic model to investigate differences in gene expression profiles related to inflammatory response and lung tumor susceptibility. The transcript profile of ~24,000 known genes was analyzed in normal lung tissue of untreated and urethane-treated AIRmax and AIRmin mice. In lungs of untreated mice, inflammation associated genes involved in pathways such as leukocyte transendothelial migration, cell adhesion and tight junctions were differentially expressed in AIRmax versus AIRmin mice. Moreover, gene expression levels differed significantly in urethane-treated mice even at 21 days after treatment. In AIRmin mice, modulation of expression of genes involved in pathways associated with inflammatory response paralleled the previously observed persistent infiltration of inflammatory cells in the lung of these mice. In conclusion, a specific gene expression profile in normal lung tissue is associated with mouse line susceptibility or resistance to lung tumorigenesis and with different inflammatory response, and urethane treatment causes a long-lasting alteration of the lung gene expression profile that correlates with persistent inflammatory response of AIRmin mice.
Transcriptome of normal lung distinguishes mouse lines with different susceptibility to inflammation and to lung tumorigenesis.
Sex, Specimen part
View SamplesUnderstanding the nature of the various glucose-derived signals for insulin secretion (both triggering and amplifying) is essential for gaining insight into the functional failure of the beta-cells in diabetes and the development of drugs for correcting this problem. The beta-cells uniquely couple changes in cellular metabolism to electrical activity and thus insulin release. In mice, beta-cell specific deletion of the von Hippel-Lindau (VHL) tumor suppressor protein leads to the activation of a HIF transcription program that includes genes involved in glycolysis, suppression of mitochondrial activity and lactate production. This reprogramming of cellular metabolism results in abnormal insulin secretion properties.
PVHL is a regulator of glucose metabolism and insulin secretion in pancreatic beta cells.
Sex, Age
View SamplesTreatments that stimulate neuronal excitability enhance motor performance after stroke.cAMP-response-element binding protein (CREB) is a transcription factor that plays a key rolein neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool ofmotor neurons enhances motor recovery after stroke, while blocking CREB signaling preventsstroke recovery. Silencing CREB-transfected neurons in the peri-infarct region with thehM4di-DREADD blocks motor recovery. Reversing this inhibition allows recovery to continue,demonstrating that it is possible to turn off and on stroke recovery by manipulating theactivity of CREB-transfected neurons. CREB transfection enhances re-mapping of injuredsomatosensory and motor circuits, and induces the formation of new connections withinthese circuits. CREB is a central molecular node in the circuit responses after stroke that leadto recovery from motor deficits.
CREB controls cortical circuit plasticity and functional recovery after stroke.
Specimen part
View SamplesMice selected for high and low acute inflammation were tested for pristane induced arthritis, showing to be susceptible and resistant, respectively.
Pristane-induced arthritis loci interact with the Slc11a1 gene to determine susceptibility in mice selected for high inflammation.
Sex, Age, Specimen part
View SamplesA mRNA expression study has been performed 20-25 minutes postmortem obtained samples from Longissimus dorsi muscle of 59 Duroc x LD/LW pigs to search for gene sequences related to meat quality (pH24, pH45, Lab colour coordinates, curing yield and exudation at three different times) or to meat composition (intramuscular fat, content of several fatty acid (C16:0, C18:0, C18:1 and C18:2), ratio of saturated, monounsaturated and polyunsaturated fatty acids, and protein and humidity contents) traits in order to find targets for selection. Gene ontology analysis, biological pathways and gene networks studies all show, that many more differentially expressed genes (506 vs 279) are related to meat quality (Group P, or perimortem characters) than to meat composition traits (Group L, or whole life traits). The difference between the number of GO terms annotated, biological pathways and gene networks in groups P and L is notable due to the differences in the complexity of the generation process of P-traits and the involvement of other tissues or organs in the generation of variability of L-traits. Also, interactions between a list of differentially expressed genes were found in ECM-receptor interaction, TGF-beta signaling pathway, fatty acid elongation in mitochondria and adipocytokine signalling pathway indicating that a substantial fraction of the gene networks could be associated with interactions between differential expressed genes related to traits under study. A high number of the most overexpressed genes are related to muscle development and functionality and repair mechanisms; they could be good candidates for breeding programs whose main goal is to enhance meat quality.
Early postmortem gene expression and its relationship to composition and quality traits in pig Longissimus dorsi muscle.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs.
Specimen part, Cell line
View SamplesThe de novo DNA methyltransferase 3-like (Dnmt3L) is a catalytically inactive DNA methylase that has been previously shown to cooperate with Dnmt3a and Dnmt3b to methylate DNA. Dnmt3L is highly expressed in mouse embryonic stem cells (ESC) but its function in these cells is unknown. We here report that Dnmt3L is required for the differentiation of ESC into primordial germ cells (PGC) through activation of the homeotic gene Rhox5. By genome-wide analysis we found that Dnmt3L is a positive regulator of methylation at gene bodies of housekeeping genes and a negative regulator of methylation at promoters of bivalent genes. We demonstrate that Dnmt3L interacts with the Polycomb PRC2 complex in competition with the DNA methyl transferases Dnmt3a and Dnmt3b to maintain low the methylation level at H3H27me3 regions. Thus in ESC, Dnmt3L counteracts the activity of de novo DNA methylases to keep low the level of DNA methylation at developmental gene promoters.
Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs.
Specimen part
View SamplesAdult mammalian CNS neurons undergo a developmental switch in intrinsic axon growth ability associated with their failure to regenerate axons after injury. Krppel-like transcription factors (KLF) regulate intrinsic axon growth ability, but signaling regulation upstream and downstream is poorly understood. Here we find that suppressing expression of KLF9, an axon growth suppressor normally upregulated 250-fold in retinal ganglion cell (RGC) development, promotes long-distance optic nerve regeneration in vivo. We identify a novel binding partner, MAPK10/JNK3, critical for KLF9s axon growth suppressive activity. Additionally, by screening genes regulated by KLFs in RGCs, we identify dual-specificity phosphatase 14 (Dusp14) as key to limiting axon growth and regenerative ability downstream of KLF9, associated with its dephosphorylation of MAPKs critical to neurotrophic signaling of RGC axon elongation. These results now link intrinsic and extrinsic regulation of axon growth and suggest new therapeutic strategies to promote axon regeneration in the adult CNS.
The Krüppel-Like Factor Gene Target Dusp14 Regulates Axon Growth and Regeneration.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a.
Specimen part, Cell line
View SamplesPhf5a regulates transcription elongation in mouse embryonic stem cells (ESCs), through regulation of the Paf1 complex.
Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a.
Specimen part, Cell line
View Samples