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GSE24614
Mus musculus
6 Downloadable Samples
Description
Mammalian genomes contain numerous DNA elements with potential transcription regulatory function but unknown target genes. We used transgenic, gain-of-function mice with an ectopic copy of the beta-globin locus control region (LCR) to better understand how regulatory elements dynamically search the genome for target genes. We find that the LCR samples a restricted nuclear sub-volume in which it forms preferential contacts with genes controlled by shared transcription factors. One contacted gene, betah1, located on another chromosome, is upregulated, providing genetic demonstration that mammalian enhancers can function between chromosomes. Upregulation is not pan-cellular but confined to selected jackpot cells significantly enriched for inter-chromosomal LCR-betah1 interactions. This implies that long-range DNA contacts are relatively stable and cell-specific and, when functional, cause variegated expression. We refer to this as spatial effect variegation (SEV). The data provide a dynamic and mechanistic framework for enhancer action, important for assigning function to the one- and three-dimensional structure of DNA.
Publication Title
Variegated gene expression caused by cell-specific long-range DNA interactions.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Rubinstein-Taybi syndrome (RSTS) is a complex autosomal-dominant disease characterized by mental and growth retardation and skeletal abnormalities. A majority of the individuals diagnosed with RSTS carry heterozygous mutation in the gene CREBBP, but a small percentage of cases are caused by mutations in EP300. To investigate the contribution of p300 to RSTS pathoetiology, we carried out a comprehensive and multidisciplinary characterization of p300+/- mice. These mice exhibited facial abnormalities and impaired growth, two traits associated to RSTS in humans. We also observed abnormal gait, reduced swimming speed, enhanced anxiety in the elevated plus maze, and mild cognitive impairment during the transfer task in the water maze. These analyses demonstratethat p300+/- mice exhibit phenotypes that are reminiscent of neurological traits observed in RSTS patients, but their comparison with previous studies on CBP deficient strains also indicate that, in agreement with the most recent findings in human patients, the activity of p300 in cognition is likely less relevant or more susceptible to compensation than the activity of CBP.
Publication Title
Syndromic features and mild cognitive impairment in mice with genetic reduction on p300 activity: Differential contribution of p300 and CBP to Rubinstein-Taybi syndrome etiology.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 4 Downloadable Samples
Description
Public information is widely available at low cost to animals living in social groups. For instance, bystanders may eavesdrop on signaling interactions between conspecifics and use it to adapt their subsequent behavior towards the observed individuals. This social eavesdropping ability is expected to require specialized mechanisms such as social attention, which selects social information available for learning. To begin exploring the genetic basis of social eavesdropping, we used a previously established attention paradigm in the lab to study the brain gene expression profile of male zebrafish in relation to the attention they have paid towards conspecifics involved or not involved in agonistic interactions. Microarray gene chips were used to characterize their brain transcriptomes based on differential expression of single genes and gene sets. These analyses were complemented by promoter region-based techniques. Using data from both approaches, we further drafted protein interaction networks. Our results suggest that attentiveness towards conspecifics, whether interacting or not, activates pathways linked to neuronal plasticity and memory formation. The network analyses suggested that fos and jun are key players on this response, and that npas4a, nr4a1 and egr4 may also play an important role.
Publication Title
Brain Transcriptomic Response to Social Eavesdropping in Zebrafish (Danio rerio).
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Most adult patients have a D816V mutation in phosphotransferase domain (PTD), we have described that half of the children carry mutations in extracellular domain (ECD). KIT-ECD versus IT-PTD-mutants were introduced into rodent Ba/F3, EML, Rat2 and human TF1 cells to investigate their biological effect. ECD- and PTD-mutants also displayed distinct whole-genome transcriptional profiles in EML cells. We observed differences in their signaling properties: they both activated STAT pathways, whereas AKT pathway was only activated by ECD-mutants. Consistently, AKT inhibitor suppressed ECD-mutant-dependent proliferation, clonogenicity and erythroid differentiation. Expression of myristoylated AKT restored erythroid differentiation in EMLPTD cells, suggesting the differential role of AKT in those mutants. Overall, our study implied different pathogenesis of pediatric versus adult mastocytosis, which might explain their diverse phenotypes.
Publication Title
Pediatric mastocytosis-associated KIT extracellular domain mutations exhibit different functional and signaling properties compared with KIT-phosphotransferase domain mutations.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Old C57BL/6 mice cannot mount an effective innate immune response
Publication Title
Aged mice are unable to mount an effective myeloid response to sepsis.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Description
In Huntingtons disease (HD), an expanded CAG repeat produces characteristic striatal neurodegeneration. Interestingly, the HD CAG repeat, whose length determines age at onset, undergoes tissue-specific somatic instability, predominant in the striatum, suggesting that tissue-specific CAG length changes could modify the disease process. Therefore, understanding the mechanisms underlying the tissue specificity of somatic instability may provide novel routes to therapies. However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors.
Publication Title
A novel approach to investigate tissue-specific trinucleotide repeat instability.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
In Huntingtons disease (HD), an expanded CAG repeat produces characteristic striatal neurodegeneration. Interestingly, the HD CAG repeat, whose length determines age at onset, undergoes tissue-specific somatic instability, predominant in the striatum, suggesting that tissue-specific CAG length changes could modify the disease process. Therefore, understanding the mechanisms underlying the tissue specificity of somatic instability may provide novel routes to therapies. However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors.
Publication Title
A novel approach to investigate tissue-specific trinucleotide repeat instability.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 69 Downloadable Samples
Description
The polytrauma (PT) murine model has unique transcriptomic responses 2 hrs, 1 day and 3 days after injury. We determined with this clinically relevant model that the increased morbidity in the elderly is secondary to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an 'emergency myelopoietic' response, engendering myeloid cells that fail to clear secondary infection. In addition, the elderly appear unable to effectively resolve their inflammatory response to severe injury.
Publication Title
A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The perinatal period and early infancy are considered critical periods for lung development, and adversities during this period are believed to impact lung health in adulthood.The main factors affecting postnatal lung development and growth include environmental exposures, cigarette smoking, (viral) infections, allergic sensitization, and asthma.Therefore, we hypothesized that concomitant exposure in the early postnatal period in mice would cause more profound alterations in lung alveolarization and growth in adult life, quantified by stereology, and differently modulate lung inflammation and gene expression than either insult alone.Five-day-old male mice were immunized intraperitoneally (i.p.) with 10 µg of ovalbumin (OVA). This procedure was repeated at the 7th day of life, animals from the control group received i.p. injection of PBS only. Mice were exposed to either ambient PM2.5 or filtered air from the 5th to the 39th day of life, using an ambient particle concentrator developed at the Harvard School of Public Health (HAPC).Total RNA of lung samples (n=3 animals per group) was extracted using RNeasy Mini Kit (Qiagen, Hilden, Germany), according to manufacturer's instructions. The microarray analysis was performed using three RNA samples for each studied group (Control, OVA, PM2.5, OVA+PM2.5), totalizing 12 samples. One hundred nanograms of total RNA was amplified with the Ambion WT Expression Kit and hybridized onto the GeneChip Mouse Gene 2.0 ST Array (Thermo Scientific, Massachusetts, USA), following manufacturer’s protocol. The comparison between the control and OVA group exhibit 32 DEGs (28 up-regulated and 4 down-regulated), between the control and PM2.5 group had 6 DEGs (4 up and 2 down) and between the control and OVA+PM2.5 group had 5 DEGs (4 up and 1 down). The comparison between OVA and PM2.5 group showed 97 DEGS (22 up and 75 down) and between OVA and OVA+PM2.5 group had 7 DEGs (4 up and 3 down). Finally, the comparison between the PM2.5 and OVA+PM2.5 group exhibit 34 DEGs (2 up and 32 down).Our experimental data provide pathological support for the hypothesis that either allergic or environmental insults in early life have permanent adverse consequences to lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice.
Publication Title
Allergic sensitization and exposure to ambient air pollution beginning early in life lead to a COPD-like phenotype in young adult mice.
Sample Metadata Fields
Treatment
View Samples