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Gene expression changes in testes from Abcg8 knockout mice compared to wild-type mice or to Abcg8 knockout mice where plant sterol entry was blocked by ezetimibe

ABSTRACT: Abcg8 knockout mice, fed chow, are infertile. These mice also are susceptible to absorption and retention of xenosterols contained in the diet. Ezetimibe, a blocker of dieary sterol entry, can reverse the fertility in Abcg8 knockout mice. In order to identify if the xenosterols resulted in disruption of a specific set of genes in the testes, we compared wild-type testes, Abcg8 knockout testes, or testes from Abcg8 knockout mice fed chow supplemented with 0.005% ezetimibe. To identify genes of interest, we reasoned that any causative gene expression changes seen in Abcg8 knockout mice fed chow, resulting in xenosterol exposure and accumulation, leading to infertilty, would be reveresed back to a pattern seen in the wild-type mice, when Abcg8 knockout mice are raised on chow containing ezetimibe (which prevents xenosterol absorption in the intestine). The target of this drug, Npc1l1, is not expressed in the testes.

ORGANISM(S): Mus musculus

PROVIDER: GSE39813 | GEO | 2012/08/02

SECONDARY ACCESSION(S): PRJNA171757

REPOSITORIES: GEO

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Gene expression changes in testes from Abcg8 knockout mice compared to wild-type mice or to Abcg8 knockout mice where plant sterol entry was blocked by ezetimibe

Project description:Abcg8 knockout mice, fed chow, are infertile. These mice also are susceptible to absorption and retention of xenosterols contained in the diet. Ezetimibe, a blocker of dieary sterol entry, can reverse the fertility in Abcg8 knockout mice. In order to identify if the xenosterols resulted in disruption of a specific set of genes in the testes, we compared wild-type testes, Abcg8 knockout testes, or testes from Abcg8 knockout mice fed chow supplemented with 0.005% ezetimibe. To identify genes of interest, we reasoned that any causative gene expression changes seen in Abcg8 knockout mice fed chow, resulting in xenosterol exposure and accumulation, leading to infertilty, would be reveresed back to a pattern seen in the wild-type mice, when Abcg8 knockout mice are raised on chow containing ezetimibe (which prevents xenosterol absorption in the intestine). The target of this drug, Npc1l1, is not expressed in the testes. Testes from wild-type mice, Abcg8 knockout mice, and Abcg8 knockout mice fed chow supplemented with ezetimibe were analyzed.

2012-08-01 | E-GEOD-39813 | biostudies-arrayexpress

Cooperation between ASTER-dependent nonvesicular transport and NPC1L1 facilitates dietary cholesterol uptake

Project description:Intestinal cholesterol absorption is an important determinant of systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1), the target of the drug ezetimibe, is a critical player in dietary cholesterol uptake. But how cholesterol moves within the cell downstream of NPC1L1 is unknown. Here we show that the nonvesicular sterol transporters Aster-B and -C cooperate with NPC1L1 to deliver dietary cholesterol from the gut lumen to the enterocyte ER for chylomicron packaging. Aster proteins are recruited to the enterocyte plasma membrane (PM) in response to NPC1L1-dependent cholesterol accumulation. Mice lacking Asters in intestine have impaired cholesterol absorption, and reduced plasma cholesterol. NanoSIMS imaging and tracer studies reveal delayed lipid trafficking into chylomicrons in Aster-deficient enterocytes. Interestingly, in addition to potently blocking NPC1L1, ezetimibe is also a low-affinity inhibitor of Aster-B and -C but not -A, and the structure of the Aster-C-ezetimibe complex reveals the basis for this selectivity. Our findings support a model in which NPC1L1 enriches dietary cholesterol at the apical PM, and ASTERs subsequently traffic this cholesterol to the ER. The findings identify the enterocyte Aster pathway as potential target for treatment of hypercholesterolemia. Alessandra Ferrari, PhD

2023-12-21 | GSE206780 | GEO

Sex differences in statin response in hypercholesterolemic (Apoe knockout) Four Core Genotypes mice.

Project description:RNA-sequening of livers from Apoe knockout Four Core Genotypes mice (XX ovaries, XX testes, XY ovaries, XY testes) fed either chow diet or chow diet + simvastatin (0.1g/kg) for 8 weeks.

2022-08-11 | GSE202977 | GEO

Gene expression changes in Ahnak knockout mice

Project description:Transcriptional profiling of WAT comparing wild-type control with Ahnak Knockout mice fed regular chow and high fat diet We obtained white adipose tissue from mice fed regular chow and high fat diet for Affymetrix microarrays

2012-04-12 | E-GEOD-37218 | biostudies-arrayexpress

Gene expression changes in Ahnak knockout mice

Project description:Transcriptional profiling of WAT comparing wild-type control with Ahnak Knockout mice fed regular chow and high fat diet

2012-04-13 | GSE37218 | GEO

Molecular Mechanisms and Targets of the Cholehepatic Drug, NorUrsodeoxycholic Acid

Project description:RNA-seq has been applied to compare the liver gene differentiation between WT mice fed with Chow and norUDCA containing diet. We aimed to determine the transporter for norUDCA absorption and circulation.

2020-02-11 | GSE145020 | GEO

NPRC deletion mitigated atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis in ApoE knockout mice

Project description:ApoE-/-mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice. Systemic NPRC knockout mice were crossed with ApoE-/- mice to generate ApoE-/-NPRC-/- mice, and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE-/-NPRC-/- versus ApoE-/- mice.

2023-07-04 | GSE233428 | GEO

Gene expression profiling in thoracic aortas of 8 week and 16 week ApoE knockout mice on a western type diet

Project description:Identification of novel pathways in the development of atherosclerosis. Here, we are looking at changes in gene expression that occur in the aorta with the development of atherosclerosis Analysis used RNA from thoracic aortas from chow fed ApoE knockout mice as control samples for comparison to the experimental samples from 8 week and 16 week ApoE knockout mice fed a western-type diet

2015-02-03 | E-GEOD-65494 | biostudies-arrayexpress

Small Heterodimer Partner and Fibroblast Growth Factor-19 Inhibit Intestinal Npc1l1 Expression and Cholesterol Absorption

Project description:Small Heterodimer Partner (SHP/NR0B2) is an unusual orphan nuclear receptor that does not have a DNA binding domain and acts as a co-repressor for many transcriptional factors, including LRH-1, SREBPs, FOXA1, and AhR, which inhibits expression of its target genes. To explore global intestinal functions of SHP, WT and SHP-KO mice were fed for 6 h after fasting overnight. In SHP-KO mice, 1,707 genes were upregulated, and 1,055 genes downregulated by 2-fold or more compared to WT mice. In GO analysis, intestinal genes upregulated with the highest significance were involved in the transport of ions, lipids, and hormones, and in cholesterol metabolic processes; whereas genes downregulated were involved in the cell cycle, the immune response, and apoptosis. Remarkably, expression of genes important for cholesterol absorption, including Npc1l1, sterol biosynthetic genes, including Hmgcr, and key intestinal bile acid transporters, Asbt and Ost-alpha/beta, was altered in SHP-KO mice compared to WT mice. Overall, in this study, SHP was shown to be a gene-specific transcriptional partner of SREBP-2 to epigenetically inhibit cholesterol-regulating genes, including Npc1l1, in the late-fed state.

2019-02-23 | GSE126939 | GEO

Transcription profiling of mouse knockouts vs wild type apoE knockout,apoA1 knockout, apoA1 transgene, apoB knockout, mice were fed normal vs artherogenic diets

Project description:Collect tissues from control C57kBL/6 and the following genetically engineered mice-apoE knockout,apoA1 knockout, apoA1 transgene, apoB knockout, LDLR knockout.Both male and female mice fed chow or atherogenic diet will be used. Animals from each group were pooled into 2 pools, one containing 4 mice and the other containing 5 mice

2010-10-10 | E-TIGR-110 | biostudies-arrayexpress

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