Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA386384 | ENA |
REPOSITORIES: ENA
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Project description:Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in liver are largely unknown. We performed microarray gene expression analysis on liver tissue of BC supplemented beta-carotene 15,150-monooxygenase 1 knockout (Bcmo1-/-) mice, which are—like humans—able to accumulate BC. This was compared with litter mates being wild-type (Bcmo1+/+) mice, and we analysed both males and females, as we previously showed that in lung tissue we observed opposite gene regulation between males and females (Van Helden et al., CMLS 2011).
2017-09-26 | GSE98846 | GEO
Project description:Nutritional effects by beta-carotene in lung in males and females of control mice versus BCMO knockout mice
| PRJNA386385 | ENA
Project description:Nutritional effects by beta-carotene versus control in lung, inguinal white adipose tissue, and liver in males and females of control wildtype mice versus BCMO/BCO1 knockout mice
| PRJNA386383 | ENA
Project description:Liver dysfunction including coagulopathy is a prominent feature of proteinenergy malnutrition. To identify mechanisms underlying malnutrition-associated coagulopathy, we administered low-protein low-fat diet to lactating dams and examined hepatic transcription and plasma coagulation parameters in young adult weanlings. Malnutrition impairs growth and liver synthetic function more severely in males versus females. Malnourished males are coagulopathic and exhibit decreased hepatocyte peroxisomes, FXR agonist bile acids, FXR binding on Fga and F11 gene regulatory elements, and coagulation factor synthesis. These effects are absent in female mice, which have low baseline levels of PPARα, suggesting that nutrient-sensing nuclear receptors regulate coagulation factor synthesis in response to host nutritional status in a sex-specific manner.
2020-10-27 | GSE156856 | GEO
Project description:Aims: We investigate sex differences and the role of oestrogen receptor beta (ERbeta) in a mouse model of pressure overload-induced myocardial hypertrophy. Methods and results: We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ER knockout (ERbeta-/-) C57Bl6 mice. All mice were characterised by echocardiography and haemodynamic measurements and were sacrificed nine weeks after surgery. Left ventricular (LV) samples were analysed by microarray profiling, real-time RT-PCR and histology. After nine weeks, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. These sex differences were abolished in ERbeta-/- mice. ERbeta deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that male WT hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than female hearts. ERbeta-/- mice exhibited a different transcriptome. Induction of pro-apoptotic genes after TAC occurred in ERbeta-/- mice of both sexes with a stronger expression in ERbeta-/- males. Histological analysis revealed, that cardiac fibrosis was more pronounced in male WT TAC than in female mice. This was abolished in ERbeta-/- mice. Apoptosis was significantly induced in both sexes of ERbeta-/- TAC mice, but it was most prominent in males. Conclusion: Female sex offers protection against ventricular chamber dilation in the TAC model. Both the female sex and ER attenuate the development of fibrosis and apoptosis; thus slowing the progression to heart failure. The influence of sex (male/female) and estrogen receptor beta expression (ERbeta knockout/wildtype) on cardiac hypertrophy (transverse aortic constriction/sham operated) was investigated. The left ventricular transcriptome of four individual mice for each combination of the three factors (sex, genotype, surgery) was detected with Affymetrix RAE 430 2.0 GeneChip arrays.
2010-01-19 | E-GEOD-18224 | biostudies-arrayexpress
Project description:In the present study, we used the Gulo-/- female and male mice model which depends entirely on ascorbate derived from the diet. Importantly, the levels of ascorbate found in the serum of Gulo-/- mice reflect the amounts of ascorbate provided in drinking water. We tested different concentrations of ascorbate ranging from 0 to 0.4% (w/v) ascorbate, added into drinking water, until the age of four months. We performed label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) global quantitative proteomic profiling to identify and quantify proteins in microsomal enriched liver extracts (MEE) from our different ascorbate treated cohorts of Gulo-/- females and males. We found that the MS intensities of several proteins in the mitochondrial complex III of the electron transport chain correlated positively with liver ascorbate concentrations in both Gulo-/- females and males. Consequently, the mitochondrial complex III activity in Gulo-/- female and male mice treated with suboptimal hepatic concentrations of ascorbate was significantly lower than Gulo-/- mice treated with optimal ascorbate concentration. Finally, proteins involved in complement activation correlated negatively with liver ascorbate concentrations in both Gulo-/- males and females.
2022-07-13 | MSV000089881 | MassIVE
Project description:HSL is a key enzyme in in the mobilization of fatty acids from the triglyceride stores of white adipose tissue. In addition, it is expressed in mice liver. In the present microarray study, changes in the transcript profile of murine liver samples due to global HSL knockout were investigated. Experiment Overall Design: Genetic modification to analyze the impact of a general knockout of the HSL gene on liver metabolism. Experiment Overall Design: HSL knockout (ko) mice versus wildtype (wt) mice. Mice fed a normal diet (ND) versus mice fed a high fat diet (FD) for 6 months. Equal amounts of liver samples from six mice were pooled and total RNA was extracted, except for HSL-null mice on FD were only 4 livers were pooled.
2009-01-14 | E-GEOD-10067 | biostudies-arrayexpress
Project description:We studied a group of melanoma patients treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n=51), and observed significantly higher rates of major pathologic response (MPR= <10% viable tumor at resection) and improved recurrence-free survival (RFS) in females versus males (MPR-66% versus 14%, p=0.001; RFS-64% versus 32% at 2 years, p=0.021). Findings were validated in a several additional cohorts 2-4 patients with unresectable metastatic melanoma treated with BRAF and/or MEK-targeted therapy (n=664 patients in total), demonstrating improved progression-free survival (PFS) and overall survival (OS) in females versus males in several of these studies. Studies in pre-clinical models demonstrated significantly impaired anti-tumor activity in male versus female BRAF/MEK-treated mice (p=0.006), with significantly higher expression of androgen receptor (AR) in tumors of male and female BRAF/MEK-treated mice versus control (p=0.0006 and 0.0025). Pharmacologic inhibition of AR signaling improved responses to BRAF/MEK-targeted therapy in male and female mice (p=0.018 and p=0.003), whereas induction of AR signaling (via testosterone administration) was associated with significantly impaired response to BRAF/MEK-targeted therapy in males and females (p=0.021 and p<0.0001).
| EGAS00001006196 | EGA
Project description:Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of cardiovascular diseases (CVDs), and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affect atherosclerosis progression in the atheroprone low-density lipoprotein receptor (LDLR) - deficient mice. In comparison to control-fed Ldlr-/- mice, β-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and plasma cholesterol levels (P = 0.0003). These changes were absent in Ldlr-/-/Bco1-/- mice, despite accumulating β-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments. Lipid production assays found that retinoic acid, the active form of vitamin A, reduced the secretion of newly synthetized triglyceride and cholesteryl ester in cell culture and mice. Overall, our findings provide insights into the role of BCO1 activity and vitamin A in atherosclerosis progression through the regulation of hepatic lipid metabolism.
2020-11-12 | GSE157972 | GEO
Project description:The purinergic receptor P2Y13 (P2RY13) has been shown to play a role in the uptake of holo-HDL particles in in vitro hepatocyte experiments. In order to determine the role of P2Y13 in lipoprotein metabolism in vivo, we ablated the expression of this gene in mice and found that P2Y13 knockout mice have lower plasma HDL (17%) and LDL (27%) levels as well as lower fecal concentrations of neutral sterols. In addition, significant decreases were detected in serum levels of fatty acids, glycerol and triglycerides in P2Y13 knockout mice. mRNA profiling analyses showed that ablation of P2Y13 affects hepatic gene expression in a gender-specific manner. Non-supervised agglomerative cluster analysis showed that expression changes in mice with the same genotype (KO or WT) cluster together and that distinct gene expression clusters can be observed for males and females. Subsequent gene set enrichment analysis showed increased expression of cholesterol and fatty acid biosynthesis genes, while fatty acid beta-oxidation genes were significantly decreased. Liver gene signatures also identified changes in SREBP-regulated and PPARgamma-regulated transcript levels. Differential gene expression upon P2RY13 gene ablation. Livers were isolated from male and female wildtype and P2RY13 knockout mice (6 per gender/genotype group, except for 5 per male/WT group). Isolated RNA was subjected to microarray analyses. The results of a one-way ANOVA analysis (p<0.05) showed 3471 transcripts whose relative expression changes were more than 20%.
2010-09-10 | E-GEOD-20920 | biostudies-arrayexpress