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Mus musculus
2 Downloadable Samples
Description
Differentiation of naive CD4 T cells into type 2 helper (Th2) cells is accompanied by chromatin remodeling and increased expression of a set of Th2-specific genes including those encoding Th2 cytokines. IL-4-mediated STAT6 activation induces high levels of transcription of GATA3, a master regulator of Th2 cell differentiation, and enforced expression of GATA3 induces Th2 cytokine expression. However, it remains unclear whether the expression of other Th2-specific genes is induced directly by GATA3. A genome-wide unbiased ChIP-seq analysis revealed that GATA3 bound to 1,279 genes selectively in Th2 cells, and 101 genes in both Th1 and Th2 cells. Simultaneously, we identified 26 highly Th2-specific STAT6-dependent inducible genes by a DNA microarray analysis-based three-step selection processes, and among them 17 genes showed GATA3 binding. We assessed dependency on GATA3 for the transcription of these 26 Th2-specific genes, and 10 genes showed increased transcription in a GATA3-dependent manner while 16 genes showed no significant responses. The transcription of the 16 GATA3-nonresponding genes was clearly increased by the introduction of an active form of STAT6, STAT6VT. Therefore, although GATA3 has been recognized as a master regulator of Th2 cell differentiation, many Th2-specific genes are not regulated by GATA3 itself but in collaboration with STAT6.
Publication Title
Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci. However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes. In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes. We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes. Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail. A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells. Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity.
Publication Title
Genome-Wide Gene Expression Profiling Revealed a Critical Role for GATA3 in the Maintenance of the Th2 Cell Identity.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Danio rerio
- 1 Downloadable Sample
Description
Our study in zebrafish is the first to use an animal model to understand the biology of the developmental disorder Roberts Syndrome (RBS). RBS is caused by mutations in the ESCO2 gene.
Publication Title
A zebrafish model of Roberts syndrome reveals that Esco2 depletion interferes with development by disrupting the cell cycle.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 39 Downloadable Samples
Description
We previously found that mice with heterozygous knockout of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII HKO mice) show various dysregulated behaviors, including cyclic variations in locomotor activity (LA), suggesting that alpha-CaMKII HKO mice may serve as an animal model showing infradian oscillation of mood. We performed gene expression microarray analysis of dentate gyrus from alpha-CaMKII HKO mice. Mice were selected for the sampling such that their LA levels varied among the mice.
Publication Title
Circadian Gene Circuitry Predicts Hyperactive Behavior in a Mood Disorder Mouse Model.
Sample Metadata Fields
Specimen part
View Samples
GSE19251- Mus musculus
- 2 Downloadable Samples
Description
High dietary fat intake is a major risk factor for the development of obesity, which is frequently associated with diabetes. To identify genes involved in diabetic nephropathy, GeneChip Expression Analysis was employed to survey the glomerular gene expression profile in diabetic KK/Ta mice fed with a high-fat diet (HFD).
Publication Title
Mindin: a novel marker for podocyte injury in diabetic nephropathy.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Several studies have shown that bone mineral density (BMD), a clinically measurable predictor of osteoporotic fracture, is the sum of genetic and environmental influences. In addition, serum IGF-1 levels have been correlated to both BMD and fracture risk. We previously identified a Quantitative Trait Locus (QTL) for Bone Mineral Density (BMD) on mouse Chromosome (Chr) 6 that overlaps a QTL for serum IGF-1. The B6.C3H-6T (6T) congenic mouse is homozygous for C57BL/6J (B6) alleles across the genome except for a 30 cM region on Chr 6 that is homozygous for C3H/HeJ (C3H) alleles. This mouse was created to study biology behind both the BMD and the serum IGF-1 QTLs and to identify the gene(s) underlying these QTLs. Female 6T mice have lower BMD and lower serum IGF-1 levels at all ages measured. As the liver is the major source of serum IGF-1, we examined differential expression in the livers of fasted female B6 and 6T mice by microarray.
Publication Title
A chromosomal inversion within a quantitative trait locus has a major effect on adipogenesis and osteoblastogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 45 Downloadable Samples
Description
Living organisms detect seasonal changes in day length (photoperiod), and alter their physiological functions accordingly, to fit seasonal environmental changes. This photoperiodic system is implicated in seasonal affective disorders and the season-associated symptoms observed in bipolar disease and schizophrenia. Thyroid-stimulating hormone beta subunit (Tshb), induced in the pars tuberalis (PT), plays a key role in the pathway that regulates animal photoperiodism. However, the upstream inducers of Tshb expression remain unknown. Here we show that late-night light stimulation acutely triggers the Eya3-Six1 pathway, which directly induces Tshb expression. Using melatonin-proficient CBA/N mice, which preserve the photoperiodic Tshb-expression response, we performed a genome-wide expression analysis of the PT under chronic short-day and long-day conditions. These data comprehensively identified long-day and short-day genes, and indicated that late-night light stimulation induces long-day genes. We verified this by advancing and extending the light period by 8 hours, which acutely induced Tshb expression, within one day. In a genome-wide expression analysis under this condition, we searched for candidate upstream genes by looking for expression that preceded Tshbs, and identified Eya3 gene. These results elucidate the comprehensive transcriptional photoperiodic response in the PT, revealing the complex regulation of Tshb expression and unexpectedly rapid response to light changes in the mammalian photoperiodic system.
Publication Title
Acute induction of Eya3 by late-night light stimulation triggers TSHβ expression in photoperiodism.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Mus musculus
- 32 Downloadable Samples
Description
Affymetrix Mouse Genome 430 2.0 arrays were used to measure genome-wide gene expression levels. The results show that high-risk human papillomavirus oncogenes E6 and E7 reprogram the cervical cancer microenvironment independently of and synergistically with estrogen, a critical co-factor in cervical cancer development and maintenance.
Publication Title
Human papillomavirus oncogenes reprogram the cervical cancer microenvironment independently of and synergistically with estrogen.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
Description
The cytosolic protein Sharpin is as a component of the linear ubiquitin chain assembly complex (LUBAC), which regulates NF-B signaling in response to specific ligands. Its inactivating mutation in Cpdm (chronic proliferative dermatitis mutation) mice causes multi-organ inflammation, yet this phenotype is not transferable into wildtype mice by hematopoietic stem cell transfer. Recent evidence demonstrated that Cpdm mice additionally display low bone mass, but the cellular and molecular causes of this phenotype remained to be established. Here we have applied non-decalcified histology together with cellular and dynamic histomorphometry to perform a thorough skeletal phenotyping of Cpdm mice. We show that Cpdm mice display trabecular and cortical osteopenia, solely explained by impaired bone formation, whereas osteoclastogenesis is unaffected. We additionally found that Cpdm mice display a severe disturbance of articular cartilage integrity in the absence of joint inflammation, supporting the concept that Sharpin-deficiency affects mesenchymal cell differentiation. Consistently, Cpdm mesenchymal cells displayed reduced osteogenic capacitiy ex vivo, yet this defect was not associated with impaired NF-B signaling. A molecular comparison of wildtype and Cpdm bone marrow cell populations further revealed that Cpdm mesenchymal cells produce higher levels of Cxcl5 and lower levels of IL1ra. Collectively, our data demonstrate that skeletal defects of Cpdm mice are not caused by chronic inflammation, but that Sharpin is as a critical regulator of mesenchymal cell differentiation and gene expression. They additionally provide an alternative molecular explanation for the inflammatory phenotype of Cpdm mice and the absence of disease transfer by hematopoetic stem cell transplantation.
Publication Title
Sharpin Controls Osteogenic Differentiation of Mesenchymal Bone Marrow Cells.
Sample Metadata Fields
Specimen part
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
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