Project description:HDAC3 is a repressor of lipogenic gene expression whereas nuclear SREBP1c is a potent activiator that is controlled by SCAP. Since these factors share many lipogenic gene targets, we sought to determine their molecular crosstalk by ChIP-sequencing. We also tested whether ectopic expression of nSREBP1c interferes with HDAC3 binding near lipognic genes. To faciliate these pulldowns, we ectoipcally expressed HA-tagged nSREBP1c in mouse livers in vivo using AAV8 viruses and the thyroxine-binding globulin promoter for hepatocyte-specifc expression. ChIP-sequencing identified over 7,000 HA-nSREBP1c binding sites, almost 50% of which were in the same vicinity as HDAC3 peaks. However, ectopic expression of nSREBP1c did not disrupt HDAC3 binding indicating that these factors indepedently bind near lipogenic genes and are regulated by distinct regulatory pathways. Gene expression changes in livers of HDAC3 liver specific knockout (LKO), SCAP LKO, and double LKO mice are provided.
Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
Project description:To investigate the differences in microRNA expression profiles between fibrotic and normal livers, we performed microRNA microarrays for total RNA extracts isolated from mouse livers treated with carbontetrachloride (CCl4) or corn-oil for 10 weeks (n=3/group). MicroRNAs were considered to have significant differences in expression level when the expression difference showed more than two-fold change between the experimental and control groups at p<0.05. We found that 12 miRNAs were differentially expressed in CCl4-induced fibrotic liver.
Project description:Analysis of gene expression profiles is an attractive method for discovering how animals respond to environmental challenges in nature. Compared to low altitudes, high altitudes are characterized by reduced partial pressures of oxygen (hypoxia) and cooler ambient temperatures To better understand how mammals cope with high altitudes, we trapped wild house mice (Mus musculus domesticus) from 3 populations in La Paz, Bolivia (3000 - 3600 m) and 3 populations in Lima, Peru (0 – 200 m). Affymetrix GeneChip® Mouse Genome 430 2.0 Arrays were use to measure mRNA abundance in the livers of these mice.
Project description:We have shown that intravenous injection of HDAC3 floxed mice with adeno-associated virus (AAV) expressing Cre depletes hepatic HDAC3, upregulates lipogenic gene expression, and causes fatty liver. When AAV-Flag-HDAC3 wild-type (WT) is co-injected along with AAV-Cre, the exogenous HDAC3 is expressed at endogenous levels and can completely rescue fatty liver phenotype. Here we profile transcriptome of the rescued WT livers in comparison with HDAC3-depleted (KO) livers. 4-months old C57BL/6 male mice were co-injected with AAV-Cre or AAV-Cre plus AAV-Flag-HDAC3. Mice were fed ad libitum and harvested at 5 pm (ZT10) at 2-weeks post-injection. Liver total RNA was extracted and hybridized to Affymetrix Mouse Gene 1.0ST array.
Project description:Analysis of gene expression profiles is an attractive method for discovering how animals respond to environmental challenges in nature. Compared to low altitudes, high altitudes are characterized by reduced partial pressures of oxygen (hypoxia) and cooler ambient temperatures To better understand how mammals cope with high altitudes, we trapped wild house mice (Mus musculus domesticus) from 3 populations in La Paz, Bolivia (3000 - 3600 m) and 3 populations in Lima, Peru (0 M-bM-^@M-^S 200 m). Affymetrix GeneChipM-BM-. Mouse Genome 430 2.0 Arrays were use to measure mRNA abundance in the livers of these mice. Eighteen male house mice were trapped from three different locations (3 mice per location)at high alttiude (La Paz, Bolivia, 3600 m) and from three locations at low altiditude (Lima, Peru, 100 m). Total mRNA was extracted from the livers and used for hybridization of Affymetrix GeneChip Mouse expression set 420.
Project description:We found that several deacetylase-dead HDAC3 mutants were able to rescue the metabolic phenotype of HDAC3-depleted livers. Here we profile the histone acetylation in the presence of different HDAC3 mutants in mouse liver. Deacetylase-dead HDAC3 mutants, including HAHA, KA, YF and HEBI, were introduced into HDAC3-depleted (Cre) mouse livers by virus along with wild-type (WT) HDAC3 as a control. Livers were harvested at 5 pm (ZT 10) and subjected to ChIP with anti-H3K9ac antibodies followed by deep sequencing.
Project description:We have shown that intravenous injection of HDAC3 floxed mice with adeno-associated virus (AAV) expressing Cre depletes hepatic HDAC3, upregulates lipogenic gene expression, and causes fatty liver. When AAV-Flag-HDAC3 wild-type (WT) is co-injected along with AAV-Cre, the exogenous HDAC3 is expressed at endogenous levels and can completely rescue fatty liver phenotype. Here we profile transcriptome of the rescued WT livers in comparison with HDAC3-depleted (KO) livers.
Project description:Sigurdsson2010 - Genome-scale metabolic model
of Mus Musculus (iMM1415)
This model is described in the article:
A detailed genome-wide
reconstruction of mouse metabolism based on human Recon 1.
Sigurdsson MI, Jamshidi N,
Steingrimsson E, Thiele I, Palsson BØ.
BMC Syst Biol 2010; 4: 140
Abstract:
BACKGROUND: Well-curated and validated network
reconstructions are extremely valuable tools in systems
biology. Detailed metabolic reconstructions of mammals have
recently emerged, including human reconstructions. They raise
the question if the various successful applications of
microbial reconstructions can be replicated in complex
organisms. RESULTS: We mapped the published, detailed
reconstruction of human metabolism (Recon 1) to other mammals.
By searching for genes homologous to Recon 1 genes within
mammalian genomes, we were able to create draft metabolic
reconstructions of five mammals, including the mouse. Each
draft reconstruction was created in compartmentalized and
non-compartmentalized version via two different approaches.
Using gap-filling algorithms, we were able to produce all
cellular components with three out of four versions of the
mouse metabolic reconstruction. We finalized a functional model
by iterative testing until it passed a predefined set of 260
validation tests. The reconstruction is the largest, most
comprehensive mouse reconstruction to-date, accounting for
1,415 genes coding for 2,212 gene-associated reactions and
1,514 non-gene-associated reactions.We tested the mouse model
for phenotype prediction capabilities. The majority of
predicted essential genes were also essential in vivo. However,
our non-tissue specific model was unable to predict gene
essentiality for many of the metabolic genes shown to be
essential in vivo. Our knockout simulation of the lipoprotein
lipase gene correlated well with experimental results,
suggesting that softer phenotypes can also be simulated.
CONCLUSIONS: We have created a high-quality mouse genome-scale
metabolic reconstruction, iMM1415 (Mus Musculus, 1415 genes).
We demonstrate that the mouse model can be used to perform
phenotype simulations, similar to models of microbe metabolism.
Since the mouse is an important experimental organism, this
model should become an essential tool for studying metabolic
phenotypes in mice, including outcomes from drug screening.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180055.
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