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GSE13106
Mus musculus
10 Downloadable Samples
Description
Phosphorylation and subsequent nuclear translocation of SMAD proteins determine the cellular response to activin. Here we identify a novel means by which activin signalling is regulated to enable developmental stage-specific SMAD gene transcription. In response to activin A, immature proliferating mouse Sertoli cells exhibit nuclear accumulation of SMAD3, but not SMAD2, although both proteins are phosphorylated. In post-mitotic differentiating cells, both SMAD2 and SMAD3 accumulate in the nucleus. Furthermore, immature Sertoli cells are sensitive to activin dosage; at higher concentrations maximal SMAD3 nuclear accumulation is observed, accompanied by a small, but significant, increase in nuclear SMAD2. Microarray analysis confirmed that differential SMAD utilization correlated with altered transcriptional outcomes and identified new activin target genes, Gja1 and Serpina5, which are known to be required for Sertoli cell development and male fertility. In immature Sertoli cells, genetic or transient knockdown of SMAD3 enhanced SMAD2 nuclear accumulation in response to activin, with increased Serpina5 mRNA levels associated with nuclear localized SMAD2. In transgenic mice with altered activin bioactivity that display male fertility phenotypes, testicular Gja1 and Serpina5 mRNA levels reflected altered in vivo activin levels. We conclude that regulated nuclear accumulation of phosphorylated SMAD2 is a novel determinant of developmentally regulated activin signalling.
Publication Title
Developmentally regulated SMAD2 and SMAD3 utilization directs activin signaling outcomes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
Description
Specific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks
Publication Title
Adaptation of myocardial substrate metabolism to a ketogenic nutrient environment.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Over expression of MHC Class l protein in skeletal muscle causes myositis. Phenotype after expression in young mice is more severe.
Publication Title
Overexpression of MHC class I heavy chain protein in young skeletal muscle leads to severe myositis: implications for juvenile myositis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Repair of injured muscle involves repair of injured myofibers through the involvement of dysferlin and its interacting partners, including annexin. Studies with mice and patients have established that dysferlin deficit leads to chronic inflammation and adipogenic replacement of the diseased muscle. However, longitudinal analysis of annexin deficit on muscle pathology and function is lacking. Here we show that unlike annexin A1, but similar to dysferlin, lack of annexin A2 (AnxA2) causes poor myofiber repair and progressive weakening with age. However, unlike dysferlin-deficient muscle, AnxA2-deficient muscles do not exhibit chronic inflammation or adipogenic replacement. Deletion of AnxA2 in dysferlin deficient mice reduces inflammation, adipogenic replacement, and loss in muscle function caused by dysferlin deficit. These results show that: a) AnxA2 facilitates myofiber repair, b) chronic inflammation and adipogenic replacement of dysferlinopathic muscle requires AnxA2, and c) inhibiting AnxA2-mediated inflammation is a novel therapeutic avenue for dysferlinopathy.
Publication Title
Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
TAZ-deficient mice have the abnormalities in the lung development. We expect the comparison of the gene expression profiles of TAZ-deficient and wild-type lungs would reveal the underlying mechanisms.
Publication Title
Transcriptional coactivator with PDZ-binding motif is essential for normal alveolarization in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus spretus, Mus musculus, Mus musculus x mus spretus
- 4 Downloadable Samples
Description
Gene expression in self-renewing epithelial tissues is controlled by cis- and trans-activating regulatory factors that mediate responses to exogenous agents capable of causing tissue damage, infection, inflammation, or tumorigenesis. We used network construction methods to analyze the genetic architecture of gene expression in normal mouse skin in a cross between tumor-susceptible Mus musculus and tumor-resistant Mus spretus. We demonstrate that gene expression motifs representing different constituent cell types within the skin such as hair follicle cells, haematopoietic cells, and melanocytes are under separate genetic control. Motifs associated with inflammation, epidermal barrier function and proliferation are differentially regulated in mice susceptible or resistant to tumor development. The intestinal stem cell marker Lgr5 is identified as a candidate master regulator of hair follicle gene expression, and the Vitamin D receptor (Vdr) links epidermal barrier function, inflammation, and tumor susceptibility.
Publication Title
Genetic architecture of mouse skin inflammation and tumour susceptibility.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Expression profile of liver of ICR mice (13-week old) treated with control diet (CRF-1) or CRF-1 containing 500 ppm diosgenin for 4 weeks.
Publication Title
Chemoprevention of azoxymethane/dextran sodium sulfate-induced mouse colon carcinogenesis by freeze-dried yam sanyaku and its constituent diosgenin.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Embryogenesis is tightly regulated by multiple levels of epigenetic systems such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent reprogramming occurs by de novo methylation and demethylation. Variance of DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analysed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions in the three germ layers and in the three adult somatic tissues are shared in common. This commonly methylated gene set is enriched in germ cell associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns with global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Taken together, our findings indicate that differentiation from ES cells to the three germ layers is accompanied by an increase in the number of commonly methylated DNA regions and that these tissue-specific alterations are present for only a small number of genes. Our findings indicate that DNA methylation at the proximal promoter regions of commonly methylated genes act as an irreversible mark which fixes somatic lineage by repressing transcription of germ cell specific genes.
Publication Title
DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Obesity resistance and increased hepatic expression of catabolism-related mRNAs in Cnot3+/- mice.
Sample Metadata Fields
Sex, Specimen part
View Samples