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Apoe ko mice

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ApoE KO mice are genetically modified mice that lack the apolipoprotein E (ApoE) gene. This gene is involved in the regulation of cholesterol and lipid metabolism. ApoE KO mice are commonly used in research to study atherosclerosis, lipoprotein metabolism, and other cardiovascular and neurological disorders.

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19 protocols using apoe ko mice

1

Dietary Fatty Acid Effects in ApoE-KO Mice

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ApoE-KO mice were originally obtained from Jackson laboratory (Bar Harbor, ME, USA). Forty 12-week-old-male mice were bred at the animal center of National Yang-Ming University. The study followed the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85–23, revised 1996) and all experimental procedures were approved by the Animal Care and Utilization Committee of National Yang-Ming University, Taipei, Taiwan. After one week on a commercial mouse chow diet, the mice were randomly allocated to one of five groups (n = 8). The control group was given normal laboratory mouse diet ad libitum and 1.1% ethanol in PBS (150 mM NaCl, 20 mM sodium phosphate, pH 7.4) by gavage every day. The other four groups were fed the same normal diet ad libitum plus 200 mg/kg of DHA, EPA, AA, or LA in 1.1% ethanol/PBS every day by gavage. After 10 weeks on the diet, the mice were fasted overnight, and their body weight was recorded. The mice were then euthanized and blood and liver samples were collected at the end of the experiment. The blood was centrifuged at 12000 g for 15 min and the plasma supernatant was then stored at −35°C until analysis. Liver tissues were harvested, washed with ice-cold isotonic saline, and stored at −80°C until use.
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2

Talin Modulator Enhances Arterial Blood Flow

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All animal experiments were approved by the Institutional Animal Care and Use Committee of Korea University College of Medicine (KOREA-2017-0126). Male, 10-week-old ApoE KO mice (#002052, The Jackson Laboratory, Bar Harbor, ME, USA) were anesthetized by intraperitoneal (IP) injection of ketamine (80 mg/kg; Yuhan, Seoul, Korea) and xylazine (8 mg/kg; Bayer, Leverkusen, Germany). After a groin incision, the left femoral arteries were injured by passing a sterile wire followed by ligation. ApoE KO mice were randomly assigned to the following 3 groups; sham (subjected to the procedure alone; n=5), vehicle control (DMSO; n=5), and talin modulator (5 mg/kg; n=6). The talin modulator and an equivalent volume of DMSO were prepared in 0.5% carboxymethylcellulose sodium salt (C5678, Sigma-Aldrich) for administration via oral gavage daily for 28 days. The mice were anesthetized at 7, 14, and 28 days post-procedure and the blood flow in the ventral side was analyzed using a laser Doppler imager (Moor Instruments, Devon, UK).
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3

Hypoxanthine Ameliorates Atherosclerosis in ApoE Knockout Mice

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Seven‐week‐old male Apoe KO mice were obtained from the Jackson Laboratories (Bar Harbor, ME, USA). C57BL/6 wild‐type (WT) mice were obtained from Samtako (O‐san, Korea). Animal experiments were approved by the Animal Care and Use Committee of Kyungpook National University and conformed to the Guide for the Care and Use of Laboratory Animals (NIH, Bethesda, MD, USA). Animals were fed with a high‐fat, high‐cholesterol diet (Research Diets, diet D12336; New Brunswick, NJ, USA) containing 16.0% fat, 1.25% cholesterol and 0.5% sodium cholic acid for 12 weeks. Fourteen WT mice were randomized into the hypoxanthine‐non‐treated (WT, n = 6) and ‐treated groups (WT‐Hx, n = 8). Another 14 Apoe KO mice were randomized into the hypoxanthine‐non‐treated (Apoe KO, n = 6) and ‐treated groups (Apoe KO‐Hx, n = 8). After 4 weeks of high‐fat diet feeding, hypoxanthine was given intraperitoneally (200 mg/kg) daily for 8 weeks. At the end of in vivo experiments (12 weeks), the animals were killed under anaesthesia breathing 1.5% isofluorane on a mask, the aortae were excised and analysed histologically. Liver was snap frozen in liquid nitrogen and stored in −80°C for lipid measurements. The blood was harvested for serum chemistry tests.
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4

Genetic Knockouts and Viral Injections in Mice

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Animal experiments were performed according to procedures approved by the Stanford University IACUC. Mice were maintained in 12 h light-dark cycles at 22°C and fed a standard irradiated rodent chow diet. All experiments on wild-type mice were performed with male C57BL/6J mice purchased from Jackson Laboratories (stock number 000664). APOE-KO mice were purchased from Jackson Laboratories (stock number 002052). Global Pm20d1 knockout mice have been previously described (Long et al., 2018 ) and are available from Jackson Laboratories (stock number 032193, MGI:6201144). For AAV injections, 7-week old male mice (C57BL/6J) were injected via tail vein at a dose of 10e10 GC/mouse diluted in saline in a total volume of 100 μl/mouse. All blood was collected into lithium heparin tubes (BD) via submandibular bleed and immediately spun (5,000 rpm, 10 min, 4°C) to isolate the plasma.
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5

HDL Nanoparticle Therapy for Atherosclerosis

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All animal work was conducted in accordance to IACUC approved protocols (NU IS00002415; approved 1/11/2016). ApoE KO mice (female, 4–6 weeks old, body weights ~20g each; Jackson Laboratories) were fed a high fat diet (42% of calories from fat, TD.88137; Envigo) for 12 weeks to induce formation of atherosclerosis. Mice were injected I.V. with 100 μL of PBS, 1 μM HDL NPs or 1 μM SNO HDL NPs 3 times per week for 6 weeks. Mice continued on the high fat diet during the 6 weeks of treatment. Following treatment, mice were euthanized and their aortas removed, cleaned and pinned for Sudan IV (Sigma Aldrich) staining. Atherosclerosis was quantified by measuring the area of the aorta and the atherosclerotic plaques, using ImageJ. JPEG images were taken of the aortas on a black background, using a variable focus dissection microscope. In ImageJ, the free hand selection tool was sued to trace the entire aorta (Area_total), which was then quantified using the Measure function. Individual plaques were then traced and their areas quantified using the Measure function (Area_athero). The percent atherosclerotic area was then calculated by: (Area_athero / Area_total) × 100. Data are presented as a percentage of total aortic area.
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6

ApoE KO Mice Experimental Procedures

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All the in vivo experimental procedures carried out in this study were performed under the principle for replacement, refinement, or reduction (the 3Rs) and in accordance with the Directive 2010/63/EU of the European Parliament and were approved by the Institutional Animal Care and Use Committee of IIS-Fundación Jimenez Diaz and Community of Madrid (PROEX 116/16 and 217/19). Male Apolipoprotein E knockout (ApoE KO) mice (Jackson Laboratory, Bar Harbor, ME, USA) were housed in ventilated cages (2–3 mice per cage) with usual bedding material and environmental enrichment in a conventional temperature-controlled room (20–22 °C) with 12 h light/dark cycle and free access to water and standard food.
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7

Atherosclerosis Imaging in ApoE-KO Mice

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For biodistribution and in vivo specificity test, C57BL/6 mice (female, 7 week old, 19–22 g weight, from Charles River Laboratories) were used. Adult ApoE-KO mice (female and male, 40–48 weeks old, 25–32 g weight, from Jackson laboratory) which are known to develop extensive atherosclerotic lesions were used for in vivo and ex vivo imaging studies. Age-matched (female and male) C57BL/6 mice were used as controls. All mice were fed a normal chow diet. Experiments were approved by the local animal care committee and were in accordance with the German Animal Welfare Act.
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8

ApoE-KO Mice Atherosclerosis Model

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All animal experiments were performed per the Institutional Animal Care and Use Committee (IACUC) Guidelines and Authorization for the Use of Laboratory Animals and were approved by the IACUC of Temple University School of Medicine. ApoE-KO mice in a wild-type (WT, C57BL/6) background were obtained from the Jackson Laboratory (Bar Harbor, ME). ApoE-KO mice were weaned at three weeks of age and given surgery and a high-fat diet (HFD) at 9 –10 weeks.
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9

Generation and Use of ApoE-KO/PGC-1α Mice

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Homozygous ApoE-KO mice and heterozygotes PGC-1α mice were crossbred and backcrossed into a murine ApoE-KO background. ApoE-KO mice and homozygous ApoE-KO/heterozygotes PGC-1α-b mice (ApoE-KO/PGC-1α mice) were obtained, and 16–20-week-old male offspring were used in experiments. All mice were maintained on a C57BL6/J background. ApoE-KO mice were obtained from The Jackson Laboratory (Bar Harbor, ME, USA)59 (link). The methods for generation of PGC-1α mice were described previously14 (link). The promoter for human α-skeletal actin, provided by Drs E. C. Hardeman and K. L. Guven (Children’s Medical Research Institute, Australia) was used to express PGC-1α-b in skeletal muscle. Animals were housed in groups of 5 mice per cage in a room with a 12-hour light/dark cycle at 22 °C and provided with standard mouse chow (CE-2, CREA Japan Inc., Tokyo, Japan) and drinking water ad libitum. Mice were cared for according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals (https://www/ncbi.nlm.nih.gov/books/NBK54050/) and our institutional guidelines. All animal experiments were approved by the Institutional Animal Care and Use Committee of the University of Shizuoka (number 165123).
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10

Angiotensin II-Induced Aortic Aneurysm in ApoE-Deficient Mice

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All procedures were approved by the Animal Care and Use Committee, Kyushu University and conducted in accordance with the institutional guidelines. ApoEKO mice were purchased from Jackson Laboratory (Bar Harbor, ME, USA). Development of AAA was induced as described previously15 (link), 16 (link)) with minor modifications17 (link)). Briefly, ApoEKO mice (12 week old male mice) were fed a HFD and administered Ang II for 4 weeks via osmotic mini pumps implanted subcutaneously. Osmotic mini pumps were implanted under anesthesia by intraperitoneal injection of ketamine (100 mg/kg) and xylazine (10 mg). At 4 weeks after the operation, the systolic blood pressure (SBP) and heart rate (HR) were measured with the tail-cuff method in a conscious state (BP-98A-L, Softron, Tokyo, Japan). Teneligliptin was given orally through drinking water and started 1 week before HFD and Ang II treatment (DPP-4i group). The approximate intake of teneligliptin was 30 mg/kg/day. The control (CTRL) group was given HFD and Ang II. The normal group was fed a normal chow.
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