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GSE27888
Mus musculus
11 Downloadable Samples
Description
Despite 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.
Publication Title
APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The gene expression of bone marrow cells of mice enriched for
Publication Title
Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
Description
The objective is to identify genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by the Rag proteins in murine pre-B cells. Cells lacking Artemis are used since the Rag-induced DSBs will not be repaired and, thus, will provide a continuous stimulus to the cell. Cells lacking Artemis and Atm are used to determine which gene expression changes depend on Atm and cells lacking Artemis that express an I kappa B alpha dominant negative are used to determine which gene expression changes depend on NFkB.
Publication Title
DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Wallerian degeneration (WD) involves the fragmentation of axonal segments disconnected from their cell bodies, segmentation of the myelin sheath, and removal of debris by Schwann cells and immune cells. The removal and downregulation of myelin-associated inhibitors of axonal regeneration and synthesis of growth factors by these two cell types are critical responses to successful nerve repair. Here, we analyzed the transcriptome of the sciatic nerve of mice carrying the Wallerian degeneration slow (WldS) mutant gene, a gene that confers axonal protection in the distal stump after injury, therefore causing significant delays in WD, neuroinflammation, and axonal regeneration.
Publication Title
Transcriptional profiling of the injured sciatic nerve of mice carrying the Wld(S) mutant gene: identification of genes involved in neuroprotection, neuroinflammation, and nerve regeneration.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Description
The efficacy and exceptionally good tolerance of estrogen blockade in the treatment of breast cancer is well recognized but novel agents are required, especially to take advantage of the multiple consecutive responses obtained in breast cancer progressing following previous hormone therapy, thus delaying the use of cytotoxic chemotherapy with its usually serious side effects. Acolbifene (ACOL) is a novel and unique antiestrogen completely free of estrogen-like activity in both the mammary gland and uterus while preventing bone loss. From the preclinical and clinical data so-far available, this new antiestrogen represents a unique opportunity for a highly potent and specific blockade of estrogen action in the mammary gland and uterus while exerting estrogen-like beneficial effects in other tissues (selective estrogen receptor modulator or SERM activity). In order to better understand the specificity of action of acolbifene, we have used Affymetrix GeneChips containing 45,000 probe sets to analyze 34,000 genes to determine the specificity of this compound compared to the pure antiestrogen fulvestrant, as well as the mixed antagonists/agonists tamoxifen and raloxifene to block the effect of estradiol (E2) and to induce effects of their own on gene expression in the mouse mammary gland. The genes modulated by E2 were those identified in two separate experiments and validated by quantitative real-time PCR (Q_RT-PCR). Three hours after the single subcutaneous injection of E2 (0.05 ug), the simultaneous administration of acolbifene, fulvestrant, tamoxifen and raloxifene blocked by 98%, 62%, 43% and 92% the number of E2-upregulated genes, respectively. On the other hand, 70%, 10%, 25% and 55% of the genes down-regulated by E2 were blocked by the same compounds. Acolbifene was also the compound which, when used alone, modulated the smallest number of genes also influenced by E2, namely 4%, thus possibly explaining the potent tumoricidal action of this compound in human breast cancer xenografts where 61% of tumors disappeared, thus bringing a new paradigm in the hormonal therapy of breast cancer.
Publication Title
Specific transcriptional response of four blockers of estrogen receptors on estradiol-modulated genes in the mouse mammary gland.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
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
- 24 Downloadable Samples
Description
The purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model) and to identify genes regulated during different stages of the disease, using RNA isolated from the joint organ and analyzed using microarrays.427 genes from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin.The results support a phasic development of OA with early matrix remodelling and transcriptional activity followed by a more quiescent period that is not maintained.
Publication Title
Disease progression and phasic changes in gene expression in a mouse model of osteoarthritis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
Description
Levels of C/EBP are low in myeloid blast crisis (BC) of chronic myelogenous leukemia (CML) and its expression in p210BCR/ABL-expressing hematopoietic cells induces granulocytic differentiation, inhibits proliferation and suppresses leukemogenesis. To assess the mechanisms involved in these effects, C/EBP targets were identified by microarray analyses. Upon C/EBP activation, expression of c-Myb and GATA-2 was repressed in 32D-BCR/ABL, K562 and CML-BC primary cells but only c-Myb levels decreased slightly in CD34+ normal progenitors. The role of these two genes for the biological effects of C/EBP was assessed by perturbing their expression in K562 cells. Expression of c-Myb blocked the proliferation inhibition and differentiation-inducing effects of C/EBP while c-Myb siRNA treatment enhanced C/EBP-mediated proliferation inhibition and induced changes in gene expression indicative of monocytic differentiation. GATA-2 expression suppressed the proliferation inhibitory effect of C/EBP but blocked in part the effect on differentiation; GATA-2 siRNA treatment had no effects on C/EBP induction of differentiation but inhibited proliferation of K562 cells, alone or upon C/EBP activation. In summary, the effects of C/EBP in p210BCR/ABL -expressing cells depend, in part, on transcriptional repression of c-Myb and GATA-2. Since perturbation of c-Myb and GATA-2 expression has non identical consequences for proliferation and differentiation of K562 cells, the effects of C/EBP appear to involve different transcription-regulated targets.
Publication Title
Transcriptional repression of c-Myb and GATA-2 is involved in the biologic effects of C/EBPalpha in p210BCR/ABL-expressing cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
Description
MicroRNAs (miRNAs) post-transcriptionally regulate the expression of thousands of distinct mRNAs. While some regulatory interactions help to maintain basal cellular functions, others are likely relevant in more specific settings, such as response to stress. Here we describe such a role for the mir-290-295 cluster, the dominant miRNA cluster in mouse embryonic stem cells (mESCs). Examination of a target list generated from bioinformatic prediction, as well as expression data following miRNA loss, revealed strong enrichment for apoptotic regulators, two of which we validated directly: Caspase 2, the most highly conserved mammalian caspase, and Ei24, a p53 transcriptional target. Consistent with these predictions, mESCs lacking miRNAs were more likely to initiate apoptosis following genotoxic exposure to gamma irradiation or doxorubicin. Knockdown of either candidate partially rescued this pro-apoptotic phenotype, as did transfection of members of the mir-290-295 cluster. These findings were recapitulated in a specific mir-290-295 deletion line, confirming that they reflect miRNA functions at physiological levels. In contrast to the basal regulatory roles previously identified, the pro-survival phenotype shown here may be most relevant to stressful gestations, where pro-oxidant metabolic states induce DNA damage. Similarly, this cluster may mediate chemotherapeutic resistance in a neoplastic context, making it a useful clinical target.
Publication Title
A latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
The Rift Valley Fever (RVF) is an arthropod-borne disease present in several countries of Africa and Middle East. It is caused by RVF virus which can infect both humans and animals. In humans, it leads to various manifestations including hepatitis, encephalitis and death, while in domestic animals it usually causes miscarriage in pregnant females and it is often fatal for the newborn. Not all people or animal infected by the virus present the same disease. Some patients exhibit unapparent or moderate febrile reactions, while others develop severe symptoms. This observation suggests that host genetic factors play a role in controlling the outcome of infection. In this work, we compare the response of two different inbred strains of mice, MBT/Pas and BALB/cByJ, to infection with RVF virus. These strains exhibit different profiles of susceptibility to RVF virus infection. Indeed, MBT/Pas mice rapidly develop high viraemia and die soon after infection, while BALB/cByJ mice have a lower viraemia and die later. Interestingly, mouse embryonic fibroblasts (MEFs) obtained from MBT/Pas foetuses allows higher viral production than BALB/cByJ MEFs.
Publication Title
A new mouse model reveals a critical role for host innate immunity in resistance to Rift Valley fever.
Sample Metadata Fields
Specimen part
View Samples