Filters
Technology
Platform
GSE18567
Mus musculus
24 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Efferent inhibition of cochlear outer hair cells is mediated by nicotinic cholinergic receptors containing alpha9 (a9) and alpha10 subunits. Mice lacking a9 nicotinic subunits fail to exhibit classic olivocochlear responses and are characterized by abnormal synaptic morphology at the base of outer hair cells. To detail molecular changes induced upon the loss of a9 subunit, we sampled cochlear RNA from wild type and a9 null mice at postnatal (P) days spanning periods of synapse formation and maturation (P3, P7, P13 and P60). Our findings point to a delay in cochlear maturation starting at the onset of hearing (P13), as well as an up-regulation of various GABA receptor subunits in adult mice lacking the a9 nicotinic subunit.
Publication Title
Lack of nAChR activity depresses cochlear maturation and up-regulates GABA system components: temporal profiling of gene expression in alpha9 null mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Purpose: The DBA/2J mouse is a model for secondary angle-closure glaucoma due to iris atrophy and pigment dispersion, which ultimately leads to increased intraocular pressure (IOP). We sought to correlate changes in retinal gene expression with glaucoma-like pathology by performing microarray analysis of retinal RNA from DBA/2J mice at 3 months before disease onset, and at 8 months, after IOP elevation. Methods: IOP was monitored monthly in DBA/2J animals by Tono-Pen and animals with normal (3 months) or elevated IOP (8 months) were identified. RNA was prepared from 3 individual retinas at each age, and the RNA was amplified and used to generate biotin-labeled probe for high density mouse Affymetrix arrays (U430.2). A subset of genes was selected for confirmation by quantitative RT-PCR using independent retina samples from DBA/2J animals at 3, 5 and 8 months of age, and compared to retinas from C57BL/6J control animals at 3 and 8 months. Results: There were changes in expression of 68 genes, with 32 genes increasing and 36 genes decreasing at 8 months versus 3 months. Upregulated genes were associated with immune response, glial activation, signaling and gene expression, while down-regulated genes included multiple crystallin genes. Significant changes in 9 upregulated genes and 2 downregulated genes were confirmed by quantitative RT-PCR, with some showing changes in expression by 5 months. Conclusions: DBA/2J retina shows evidence for glial activation and an immune-related response following IOP elevation, similar to what has been reported following acute elevation of IOP in other models.
Publication Title
Microarray analysis of retinal gene expression in the DBA/2J model of glaucoma.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Xbp1 is a major transcription factor in the unfolded protein response. To uncover its function in DCs we generated a conditional KO for Xbp1 in dendritic cells. We here compare the expression of mRNAs in two different splenic DC subpopulations, CD8a and CD11b DCs in both WT and KO mice.
Publication Title
The unfolded-protein-response sensor IRE-1α regulates the function of CD8α+ dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
Illumina HiSeq 2500
Description
Microglia have important remodeling functions in development and disease. There is evidence for molecular diversity of microglia suggesting they may exist in distinct functional states to differentially impact CNS health and function. To better understand this in development, we profiled microglia of a discrete developing CNS region, the murine retina. We find that retinal microglia transition through unique transcriptional states and identify a population with peak density postnatally that resemble adult disease-associated microglia (DAM) and CD11c+ microglia of developing white matter, we term DAM-like. Developmental cell death is a major driver of the DAM-like phenotype, and TREM2 signaling is required for select DAM gene expression. Notably, DAM-like cells that highly express CD11c are not dependent on CSF1R signaling for survival, and TREM2 signaling is required for CSF1R independence in a subset of microglia. Thus, microglial phenotype in development is influenced by local developmental events and may share features with microglia in disease. Overall design: mRNA profiles of whole retina and sorted retinal microglia from embryonic day (e)16.5, postnatal day (P)7 and adult (P60) mice were generated by deep sequencing.
Publication Title
Developmental Apoptosis Promotes a Disease-Related Gene Signature and Independence from CSF1R Signaling in Retinal Microglia.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
We investigated the gene expression profile changes after Ezh2 conditional knockout in the mouse retina at E16.5. Loss of Ezh2 leads to up-regulation of PRC2 targeted genes including cell cycle regulators and multiple genes which are not normally expressed in the retina, including many Hox genes. Loss of Ezh2 resulted in a dramatic decline in progenitor proliferation by postnatal day 3, such that there is an early end to neurogenesis, and disruption of laminar organization. Although there are only minor effects on embryonic retinal development, there is accelerated differentiation of several late born cell types postnatally, including photoreceptors and Mueller glia, which become reactive by postnatal day 14. Overall design: Peripheral retina was dissected at E16.5 from Pax6alpha-Cre:Ezh2fl/+ and Pax6alpha-Cre:Ezh2fl/null mouse embryos. Total RNA was purified and RNA deep sequencing was done using 4 controls and 4 conditional knockout samples.
Publication Title
Ezh2 maintains retinal progenitor proliferation, transcriptional integrity, and the timing of late differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
The purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa to alter metabolism in the F1 and F2 generation offspring
Publication Title
High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
RhoGDIbeta (ARHGDIB) is often expressed in tumor cells. It negatively regulates Rho-GTPases, but may have other functions as well. To analyze its effect on gene expression, RhoGDIbeta was suppressed by RNA interference in MDA-MB-231 breast cancer cells and changes in gene expression monitored by cDNA microarrays.
Publication Title
Cyclooxygenase-2 is a target gene of rho GDP dissociation inhibitor beta in breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The translocation t(10,11)(p13;q14) resulting in the formation of the CALM/AF10 fusion gene is involved in various hematological malignancies including acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and malignant lymphoma and is usually associated with poor prognosis. We established a knock-in mouse model allowing tissue-specific CALM/AF10 expression from the Rosa26 locus using a loxP-STOP-loxP cassette to study leukemic transformation by the CALM/AF10 fusion protein during hematopoiesis. vav-Cre induced pan-hematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Leukemias were either myeloid or had myeloid feature and showed expression of the B cell marker B220. Gene expression profiling of leukemic bone marrow cells revealed the overexpression of Hoxa cluster genes and the Hox co-factor Meis1. The long latency to leukemia development suggested that additional, collaborative genetic lesions are required. We identified an average of 2 to 3 additional mutations per leukemia using whole-exome sequencing. When CALM/AF10 was expressed in the B lymphoid compartment using mb1-Cre or CD19-Cre inducer lines no leukemia development was observed. Our results indicate that CALM/AF10 needs to be expressed from the stem or early progenitor cell stage onward to permit the acquisition of additional mutations required for leukemic transformation.
Publication Title
The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2000
Description
Through the generation of humanized FUS mice expressing full length human FUS, we identify that when expressed at near endogenous murine FUS levels both wild-type or ALS- and frontotemporal dementia (FTD)-causing mutations complement the essential function(s) of murine FUS. Replacement of murine FUS with mutant, but not wild-type, human FUS causes stress-mediated induction of chaperones, decreased expression of ion channels/transporters essential for synaptic function, and reduced synaptic activity, without loss of nuclear FUS or its cytoplasmic aggregation. Most strikingly, accumulation of mutant human FUS is shown to activate an integrated stress response and inhibit local, intra-axonal protein synthesis in hippocampal neurons and sciatic nerves. Collectively, our evidence demonstrates that human ALS/FTD-linked mutations in FUS induce a gain-of-toxicity that includes stress-mediated suppression in intra-axonal translation, synaptic dysfunction, and progressive, age-dependent motor and cognitive disease without cytoplasmic aggregation, altered nuclear localization, or aberrant splicing of FUS-bound pre-mRNAs. Methods: RNA from mouse spinal cords of 18-month-old mFUS-/-/hgFUS (WT, R521C or R521H) and their Non-Tg control littermates was extracted with TRIzol. RNA quality was measured using the Agilent Bioanalyzer system and processed using the Illumina TruSeq Stranded mRNA Sample Preparation Kit according to manufacturer's protocols. mRNA profiles were generated by deep sequencing, with n=3 biological replicates per group. Results: We mapped on average 15 million non-redundant reads per sample. Fastq files were aligned to mouse reference genome (mm9 UCSC Genome Browser) using TopHat workfow and the transcript abundance for each annotated protein-coding gene [as fragments per kilobase of transcript per million mapped reads (FPKM)] was estimated by Cufflinks. 13,468 genes which expressed FPKM>=1 were kept for downstream analyses. RNA profiles from normal (Non-Tg) and humanized hgFUSWT mice were almost undistinguishable. Both humanized mutant FUS lines had highly distinct RNA profiles [determined with unsupervised hierarchical clustering and principal component analysis (PCA)], with 709 down and 348 up-regulated genes relative to age-matched Non-Tg or humanized hgFUSWT littermates (P<0.05). These changes uncovered FUS mutant dependent altered pathways that may contribute to ALS/FTD-linked mutant FUS-mediated toxicity. The validation by RT-QPCR of altered expression of 20 genes is shown in Figure 5. Overall design: RNA expression profile of mouse spinal cords from 18-month-old mFUS-/-/hgFUS (WT, R521C or R521H) and their Non-Tg control littermates was obtained by deep sequencing in n=3 indendepent animals per genotype using Illumina HiSeq 2000 sequencer.
Publication Title
ALS/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Expression of insulin in terminally differentiated non-beta pancreatic cell types could be important for treating type-1 diabetes. We observed that the kinase inhibitor GW8510 up-regulated insulin expression in mouse pancreatic alpha cells.
Publication Title
GW8510 increases insulin expression in pancreatic alpha cells through activation of p53 transcriptional activity.
Sample Metadata Fields
Cell line, Compound
View Samples