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GSE9444
Mus musculus
93 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Homer1a is a core brain molecular correlate of sleep loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 108 Downloadable Samples
Description
Copy number variation (CNV) of DNA segments has recently been identified as a major source of genetic diversity, but a more comprehensive understanding of the extent and phenotypic effect of this type of variation is only beginning to emerge. In this study we generated genome-wide expression data from 6 mouse tissues to investigate how CNVs influence gene expression.
Publication Title
Segmental copy number variation shapes tissue transcriptomes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 69 Downloadable Samples
Description
These studies adress differential changes in gene expression between sleep deprived and control mice. We profiled gene expression at four time points across the 24H Light/Dark cycle to take into account circadian influences and used three different inbred strains to understand the influence of genetic background.
Publication Title
Homer1a is a core brain molecular correlate of sleep loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Description
To gain insight into the molecular changes of sleep need, this study addresses gene expression changes in a subpopulation of neurons selectively activated by sleep deprivation. Whole brain expression analyses after 6h sleep deprivation clearly indicate that Homer1a is the best index of sleep need, consistently in all mouse strains analyzed. Transgenic mice expressing a FLAG-tagged poly(A)-binding protein (PABP) under the control of Homer1a promoter were generated. Because PABP binds the poly(A) tails of mRNA, affinity purification of FLAG-tagged PABP proteins from whole brain lysates, is expected to co-precipitate all mRNAs from neurons expressing Homer1a. Three other activity-induced genes (Ptgs2, Jph3, and Nptx2) were identified by this technique to be over-expressed after sleep loss. All four genes play a role in recovery from glutamate-induced neuronal hyperactivity. The consistent activation of Homer1a suggests a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness.
Publication Title
Homer1a is a core brain molecular correlate of sleep loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
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
Publication Title
Abnormal social behaviors and altered gene expression rates in a mouse model for Potocki-Lupski syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 72 Downloadable Samples
Description
A preliminary understanding of the phenotypic effect of copy number variation (CNV) of DNA segments is emerging. These rearrangements were demonstrated to influence, in a somewhat dose-dependent manner, the expression of genes mapping within. They were shown to also affect the expression of genes located on their flanks, sometimes at great distance. Here, we show by monitoring these effects at multiple life stages, that these controls over expression are effective throughout mouse development. Similarly, we observe that the more specific spatial expression patterns of CNV genes are maintained throughout life. However, we find that some brain-expressed genes appear to be under compensatory loops only at specific time-points, indicating that the influence of CNVs on these genes is modulated through development. We also observe that CNV genes are significantly enriched upon transcripts that show variable time-course of expression in different strains. Thus modifying the number of copy of a gene not only potentially alters its expression level, but possibly also its time of expression.
Publication Title
Copy number variation modifies expression time courses.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 61 Downloadable Samples
Description
To study the effect of structural changes on expression, we assessed gene expression in genomic disorder mouse models. Both a microdeletion and its reciprocal microduplication mapping to mouse chromosome 11 (MMU11), which model the rearrangements present in Smith-Magenis (SMS) and Potocki-Lupski (PTLS) syndromes patients, respectively, have been engineered. We profiled the transcriptome of five different tissues affected in human patients in mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+) and uniallelic 2n (Deletion/Duplication) copies of the same region in an identical genetic background. The most differentially expressed transcripts between the four studied genotypes were ranked. A highly significant propensity, are mapping to the engineered SMS/PTLS interval in the different tissues. A statistically significant overrepresentation of the genes mapping to the flanks of the engineered interval was also found in the top-ranked differentially expressed genes. A phenomenon efficient across multiple cell lineages and that extends along the entire length of the chromosome, tens of megabases from the breakpoints. These long-range effects are unidirectional and uncoupled from the number of copies of the copy number variation (CNV) genes. Thus, our results suggest that the assortment of genes mapping to a chromosome is not random. They also indicate that a structural change at a given position of the human genome may cause the same perturbation in particular pathways regardless of gene dosage. An issue that should be considered in appreciating the contribution of this class of variation to phenotypic features.
Publication Title
No associated publication
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 24 Downloadable Samples
Description
Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.
Publication Title
Molecular clock is involved in predictive circadian adjustment of renal function.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
Description
Most metabolic studies are conducted in male animals; thus, the molecular mechanism controlling gender-specific pathways has been neglected, including sex-dependent responses to peroxisome proliferator-activated receptors (PPARs). Here we show that PPARalpha has broad female-dependent repressive actions on hepatic genes involved in steroid metabolism and inflammation. In males, this effect is reproduced by the administration of synthetic PPARalpha ligand. Using the steroid hydroxylase gene Cyp7b1 as a model, we elucidated the molecular mechanism of this PPARalpha-dependent repression. Initial sumoylation of the ligand-binding domain of PPARalpha triggers the interaction of PPARalpha with the GA-binding protein alpha bound to the target promoter. Histone deacetylase is then recruited, and histones and adjacent Sp1-binding site are methylated. These events result in the loss of Sp1-stimulated expression, and thus the down-regulation of Cyp7b1. Physiologically, this repression confers protection against estrogen-induced intrahepatic cholestasis, paving the way for a novel therapy against the most common hepatic disease during pregnancy.
Publication Title
Sumoylated PPARalpha mediates sex-specific gene repression and protects the liver from estrogen-induced toxicity in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
Description
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and attacks of muscle atonia triggered by strong emotions (cataplexy). The best biological marker of narcolepsy is orexin deficiency with dramatic loss in hypothalamic orexin-producing neurons. Together with a tight HLA and T-cell receptor alpha(5) association, narcolepsy is believed to be autoimmune although all attempts to prove it have failed.To characterize orexin specific peptides we produced a transgenic mouse model to access to the orexin neurons transcription profile. We generated BAC-based transgenic mice by replacing the orexin coding sequence by a flag-tagged poly(A) binding protein (Pabp1) cDNA sequence. The basis of this construct is to take advantage of the ability of Pabp1 to bind to the poly(A) tails of mRNAs in vivo. Thus mRNAs from orexin cells are expected to be enriched by cross-linking them to the flag-tagged PABP and then co-immunoprecipitating this complex with a specific anti-flag monoclonal antibody.
Publication Title
Elevated Tribbles homolog 2-specific antibody levels in narcolepsy patients.
Sample Metadata Fields
Age
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