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GSE25926
Mus musculus
14 Downloadable Samples
Description
The -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.
Publication Title
Comparative transcriptome profiling of amyloid precursor protein family members in the adult cortex.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Description
Cellular signal transduction is governed by multiple feedback mechanisms to elicit robust cellular decisions. We combined mathematical modeling and extensive time-resolved data sets in primary erythroid progenitor cells and dissected the roles of the two transcriptional feedback regulators of the SOCS family, CIS and SOCS3 in JAK2/STAT5 signaling. Our model revealed that both feedbacks are most effective at different ligand concentration ranges.
Publication Title
Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
PPAR is known for its anti-inflammatory actions in macrophages. However, which macrophage populations express PPAR in vivo and how it regulates tissue homeostasis in the steady state and during inflammation is not completely understood. We show that lung and spleen macrophages constitutively expressed PPAR, while other macrophage populations did not. Recruitment of monocytes to sites of inflammation was associated with induction of PPAR as they differentiated to macrophages. Its absence in these macrophages led to failed resolution of inflammation, characterized by persistent, low-level recruitment of leukocytes. Conversely, PPAR agonists supported an earlier cessation in leukocyte recruitment during resolution of acute inflammation and likewise suppressed monocyte recruitment to chronically inflamed atherosclerotic vessels. In the steady state, PPAR deficiency in macrophages had no obvious impact in the spleen but profoundly altered cellular lipid homeostasis in lung macrophages. Reminiscent of pulmonary alveolar proteinosis, LysM-Cre x PPARflox/flox mice displayed mild leukocytic inflammation in the steady-state lung and succumbed faster to mortality upon infection with S. pneumoniae. Surprisingly, this mortality was not due to overly exuberant inflammation, but instead to impaired bacterial clearance. Thus, in addition to its anti-inflammatory role in promoting resolution of inflammation, PPAR sustains functionality in lung macrophages and thereby has a pivotal role in supporting pulmonary host defense.
Publication Title
Systemic analysis of PPARγ in mouse macrophage populations reveals marked diversity in expression with critical roles in resolution of inflammation and airway immunity.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Noroviruses have been widely recognized for their importance as causative agents of non-bacterial gastroenteritis. Mouse norovirus is the only representative of the norovirus genus, family Caliciviridae, able to grow in cell culture. The aim of this study is to describe the differences in the expression profiles of MNV-1 and mock-infected macrophages (RAW 264.7 cells), in order to better understand the response of the host cell to norovirus infection.
Publication Title
Apoptosis in murine norovirus-infected RAW264.7 cells is associated with downregulation of survivin.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of the cortical neurons that mediate antidepressant responses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 23 Downloadable Samples
Description
NOD mice are an inbred strain that display enhanced MZ B cell differentiation from an early age. Interestingly, several lines of evidence implicate MZ B cells in this strain as important contributors to the T cell mediated beta cell destruction associated with the development of type 1 diabetes (T1D). In order to develop a better understanding of the underlying causes for augmented MZ B cell production in NOD mice, we obtained the transcriptional profiles of FO and MZ subsets and TR precursors from NOD mice and compared them to those of the B6 strain.
Publication Title
Intrinsic molecular factors cause aberrant expansion of the splenic marginal zone B cell population in nonobese diabetic mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Our laboratory wanted to define the transcription profile of aged skeletal muscle. For this reason, we performed a triplicate microarray study on young (3 weeks) and aged (24 months) gatrocnemius muscle from wild-type C57B16 Mice
Publication Title
Transcriptional profiling of skeletal muscle reveals factors that are necessary to maintain satellite cell integrity during ageing.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 71 Downloadable Samples
Description
Goal of the experiment: Analysis of gene expression changes in the cortex, striatum, hippocampus, hypothalamus, Drd2-MSNs and Drd1-MSNs of mice with a postnatal, neuron-specific ablation of GLP or G9a as compared to control mice.
Publication Title
Control of cognition and adaptive behavior by the GLP/G9a epigenetic suppressor complex.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 42 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Activity-dependent regulation of inhibitory synapse development by Npas4.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Description
To identify the activity-induced gene expression programs in inhibitory and excitatory neurons, we analyzed RNA extracted from cultured E14 mouse MGE- and CTX-derived neurons (DIV 10) after these cultures were membrane-depolarized for 0, 1 and 6 hrs with 55mM extracellular KCl. To identify the gene programs regulated in these cells by the activity-induced early-response transcription factor Npas4, we repeated the same experiment in the MGE- and CTX-cultures lacking Npas4 (Npas4-KO).
Publication Title
Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples