Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1010236 | ENA |
REPOSITORIES: ENA
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Project description:To investigate the role of human CYP2B6 in vivo under high-fat diet conditions, we compared our previously developed Cyp2b triple knockout mouse lacking Cyp2b9, Cyp2b10, and Cyp2b13 (via CRISPER/Cas9; Cyp2b-null), to our newly developed humanized-CYP2B6-transgenic (hCYP2B6-Tg) mouse model (on a Cyp2b-null background). hCYP2B6-Tg and Cyp2b-null mice were fed a high-fat diet consisting of 60% fat for 16 weeks. RNA was extracted from the livers of female and male mice from both treatment groups and used for RNA seqencing. RNAseq and in gene ontology (GO) analysis indicate human CYP2B6 is important in protein processing and phosphorylation, hepatic circadian regulation, and lipid metabolism under HFD conditions.Circadian rhythm-associated genes were up-regulated in HFD-fed hCYP2B6-Tg mice compared to Cyp2b-null mice. Circadian regulation plays an important role in liver metabolism and metabolic disease. In addition, female hCYP2B6-Tg mice had several down-regulated genes involved in lipid metabolism compared to Cyp2b-null mice, notably Angptl8 (logFC = -1.24), a critical modulator of lipid metabolism that has been associated with metabolic disease. Genes identified by RNAseq analysis may contribute to the overall healthier metabolic profile of HFD-fed humanized mice compared to Cyp2b-null mice.
2020-06-01 | GSE148460 | GEO
Project description:MECP2-R270X transgenic mice (TG) and MECP2-G273X TG mice were generated in the Zoghbi Lab. These mice express the respective truncated form of MeCP2 tagged with GFP at the C-terminus from a transgenic human PAC containing all known regulatory sequences. These transgenes were maintained on a wild-type pure FVB background. For experiments each transgenic line was crossed by Mecp2 null mice (Mecp2 tm1.1Bird) on a pure 129SvEv background and the resulting male F1 hybrid progeny (FVB;129SvEv) that lacked endogenous MeCP2 expression but expressed either transgene (Mecp2 -/y; MECP2-R270X TG or Mecp2-/y; MECP2-G273X TG) were used for ChIP-Seq analysis. Whole brain from either the R270X mice (Mecp2 -/y; MECP2-R270X TG) or the G273X mice (Mecp2 -/y; MECP2-G273X TG) was formaldehyde crosslinked and purified chromatin was immunoprecipitated with anti-GFP antibody (Abcam ab6556). 2 samples: R270X (Mecp2 -/y; MECP2-R270X TG) and G273X (Mecp2 -/y; MECP2-G273X TG) both on an F1 (FVB;129SvEv) hybrid background
2013-03-12 | E-GEOD-36536 | biostudies-arrayexpress
Project description:MECP2-R270X transgenic mice (TG) and MECP2-G273X TG mice were generated in the Zoghbi Lab. These mice express the respective truncated form of MeCP2 tagged with GFP at the C-terminus from a transgenic human PAC containing all known regulatory sequences. These transgenes were maintained on a wild-type pure FVB background. For experiments each transgenic line was crossed by Mecp2 null mice (Mecp2 tm1.1Bird) on a pure 129SvEv background and the resulting male F1 hybrid progeny (FVB;129SvEv) that lacked endogenous MeCP2 expression but expressed either transgene (Mecp2 -/y; MECP2-R270X TG or Mecp2-/y; MECP2-G273X TG) were used for ChIP-Seq analysis. Whole brain from either the R270X mice (Mecp2 -/y; MECP2-R270X TG) or the G273X mice (Mecp2 -/y; MECP2-G273X TG) was formaldehyde crosslinked and purified chromatin was immunoprecipitated with anti-GFP antibody (Abcam ab6556).
2013-03-12 | GSE36536 | GEO
Project description:To elucidate the molecular mechanisms behind corneal angiogenesis in Dscr-1-/- mice, we performed microarray analysis using intact corneas from B6, Dscr-1-/- mice, ApoE-/- mice, Dscr-1-/- and ApoE-/- double null mutant mice and sutured corneas from B6, Dscr-1-/- and Dscr-1 Tg mouse.
2020-04-01 | GSE130040 | GEO
Project description:Perfluorooctanesulfonate (PFOS) is a widespread environmental pollutant with a long half-life and clearly negative outcomes on metabolic diseases such as fatty liver and diabetes. Male and female Cyp2b-null and humanized CYP2B6-transgenic (hCYP2B6-Tg) mice were treated with 0, 1, or 10 mg/kg/day PFOS for 21 days, and surprisingly it was found that PFOS was retained at greater concentrations in the serum and liver of hCYP2B6-Tg mice than Cyp2b-null mice with greater differences in the females. Thus, Cyp2b-null and hCYP2B6-Tg mice provide new models for investigating individual mechanisms for PFOS bioaccumulation and toxicity. Overt toxicity was greater in hCYP2B6-Tg mice (especially females) as measured by mortality; however, steato-sis occurred more readily in Cyp2b-null mice despite the lower PFOS liver concentrations. Tar-geted lipidomics and transcriptomics from PFOS treated Cyp2b-null and hCYP2B6-Tg mouse livers were performed and compared to PFOS retention and serum markers of toxicity by PCA. Several oxylipins, including prostaglandins, thromboxanes, and docosahexaenoic acid metabo-lites are associated or inversely associated with PFOS toxicity. Both lipidomics and tran-scriptomics indicate PFOS toxicity is associated with PPAR activity in all models. GO terms as-sociated with reduced steatosis were sexually dimorphic with lipid metabolism and transport increased in females and circadian rhythm associated genes increased in males. However, we can rule out that steatosis was initially protective from PFOS toxicity. Moreover, several transporters are associated with increased retention probably due to increased uptake. The strongest associa-tions are the organic anion transport proteins (Oatp1a4-6) genes and a long-chain fatty acid transport protein (fatp1), enriched in female hCYP2B6-Tg mice. PFOS uptake was also reduced in cultured murine hepatocytes by OATP inhibitors. The role of OATP1A6 and FATP1 in PFOS transport has not been tested. In summary, Cyp2b-null and hCYP2B6-Tg mice provided unique models for estimating the importance of novel mechanisms in PFOS retention and toxicity.
2024-01-31 | GSE249617 | GEO
Project description:Purpose: Analyze the transcriptomic differences between hepatic non parenchimal cells (HNPCs) of Non-Tg and Fgf18 Tg mice Methods: Fresh isolated HNPCs suspensions of Non-Tg and Fgf18 Tg were loaded on the BD RhapsodyTM Single-Cell Analysis System Results: We revealed that CD31-CD34+ cells comprise Lrat+ hepatic stellate cells (HSCs), Acta2+ myofibroblasts, and Thy1+ portal fibroblasts.
2023-09-20 | GSE205871 | GEO
Project description:Notch3 is a transmembrane receptor which is critically important for the structure and myogenic response of distal arteries, particularly cerebral arteries. After activation of the receptor, the intracellular domain translocates in the nucleus to activate target genes transcription. In order to identify Notch3 target genes, we used microarrays to compare gene expression from caudal arteries (Notch3+/+ vs Notch3-/-) and selected down-regulated genes in Notch3-/- arteries. Caudal arteries were dissected from 1 month old Notch3+/+ and Notch3-/- mice. RNA was prepared with arteries pooled from three (AJ_N3WT_3, AJ_N3WT_4) or four (AJ_N3WT_1, AJ_N3KO_1, AJ_N3KO_2, AJ_N3KO_4) mice and hybridized on Mouse MOE430.2 Affymetrix chips. For each group (Notch3+/+ and Notch3-/-), three biological replicates were performed.
2012-03-30 | E-GEOD-36437 | biostudies-arrayexpress
Project description:Transcriptomic analyses of ChREBPtotal-null mice and ChREBPβ-null mice
| PRJNA744196 | ENA
Project description:Transcriptomic analyses of ChREBPtotal-null mice and ChREBPβ-null mice liver
| PRJNA744205 | ENA