Project description:Identification of causal genes for atherosclerosis in a segregating mouse population and validation via single-gene knockout and plaque progression mouse models. This SuperSeries is composed of the following subset Series: GSE18442: Aortic arch profiling of Ldlr knockout mice with human CETP transgene GSE18443: Aortic arch profiling of Apoe knockout mice Refer to individual Series
Project description:Increased serum apoB and associated low density lipoprotein cholesterol (LDL) levels are well correlated with an increased risk of coronary disease. Apo E-/- and LDLr -/- mice have been extensively used for studies of coronary atherosclerosis. These animals show atherosclerotic lesions similar to those in humans, but their serum lipids are low in apoB containing LDL particles. We describe the development of a new mouse model with a human-like lipid profile. Ldlr+/- CETP+/- hemizygous mice carry a single copy of the human CETP transgene and a single copy of a LDL receptor mutation. To evaluate the apoB pathways in this mouse model, we used novel siRNAs formulated in lipid nanoparticles (LNPs). ApoB siRNAs induced up to 95% reduction of liver ApoB mRNA and serum apoB protein, and a significant lowering of serum LDL in Ldlr+/- CETP+/- mice. ApoB targeting is specific, dose dependent and shows lipid lowering effects for over three weeks. Although specific TGs were affected by ApoB KD, and the total plasma lipid levels were decreased by 70%, the overall lipid distribution did not change. Results presented here demonstrate a new mouse model for investigating additional targets within the ApoB pathways using the siRNA modality. Two oligoes specific for ApoB were used to knock down apoB expression in C57Bl6 or B6-Ldlr(tm1)Tg(APOA1-CETP) mice. Gene expression profiling was performed with Affymetrix Merck Custom Mouse 1.0 microarrays (GPL9734).
Project description:Aortic arch profiling of Ldlr-/- huCETP transgenic mice fed a low fat, cholesterol-containing western diet (LFWD, 9% fat, 0.15% cholesterol) starting at 8 weeks of age for 4, 8, 12, and 16 weeks.
Project description:Gene expression profiles from the aortic arch of Ldlr-/-Apob100/100 Mttpflox/flox Mx1-Cre mice at different stages of atherosclerosis development Total RNAs from the aortic arch were collected at different time points during atherosclerosis development (10, 20, 30, 40, 50, and 60 weeks of age), 4-7 mice per time point.
Project description:Aortic arch profiling of Ldlr-/- huCETP transgenic mice fed a low fat, cholesterol-containing western diet (LFWD, 9% fat, 0.15% cholesterol) starting at 8 weeks of age for 4, 8, 12, and 16 weeks. Ldlr-/- huCETP transgenic mice were fed a low fat, cholesterol-containing western diet (LFWD, 9% fat, 0.15% cholesterol) starting at 8 weeks of age for 4, 8, 12, and 16 weeks (Supplementary Figure 1). At each time point, 10 mice were studied. Mice were euthanized at each time point and the aortic arch of each mouse was immediately collected and flash-frozen in liquid N2. Mice were fasted overnight prior to euthanasia. the aortic arches of 10 mice in the same study group were pooled for profiling, resulting in one pool per study group. Tissues were homogenized and total RNA was extracted. The control RNA pool was composed of equal aliquots of RNA derived from the 4 pools (40 samples) from the LFWD 4-, 8-, 12- and 16-week time points.
Project description:Gene expression profiles from the aortic arch of Ldlr-/-Apob100/100 Mttpflox/flox Mx1-Cre mice at different stages of atherosclerosis development
Project description:Increased serum apoB and associated low density lipoprotein cholesterol (LDL) levels are well correlated with an increased risk of coronary disease. Apo E-/- and LDLr -/- mice have been extensively used for studies of coronary atherosclerosis. These animals show atherosclerotic lesions similar to those in humans, but their serum lipids are low in apoB containing LDL particles. We describe the development of a new mouse model with a human-like lipid profile. Ldlr+/- CETP+/- hemizygous mice carry a single copy of the human CETP transgene and a single copy of a LDL receptor mutation. To evaluate the apoB pathways in this mouse model, we used novel siRNAs formulated in lipid nanoparticles (LNPs). ApoB siRNAs induced up to 95% reduction of liver ApoB mRNA and serum apoB protein, and a significant lowering of serum LDL in Ldlr+/- CETP+/- mice. ApoB targeting is specific, dose dependent and shows lipid lowering effects for over three weeks. Although specific TGs were affected by ApoB KD, and the total plasma lipid levels were decreased by 70%, the overall lipid distribution did not change. Results presented here demonstrate a new mouse model for investigating additional targets within the ApoB pathways using the siRNA modality.
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
Project description:Aortic tissues of developing and established aneurysms produced by angiotensin II (AngII) infusion were examined in Apoe-/- and Ldlr-/- mice. Aortas were also acquired from wildtype C57BL/6J mice following intraluminal elastase incubation. Aortas were dissected free and separated into eight anatomical segments for proteomics in comparison to their appropriate controls. In addition, proteomics was performed on human infrarenal aortic aneurysm tissues as well as aortic tissue collected from age-matched controls.
