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16 protocols using taup301l

1

Alzheimer's Disease Progression in Transgenic Mice

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Wild-type (C57BL/6 or B6) and 3xTg-AD mice [B6; 129-Psen1tm1Mpm Tg(APP-Swe, TauP301L)1Lfa/Mmjax] expressing three mutant genes, namely Psen1-M146V, APP-K670N/M671L, and Tau-P301L, were obtained from the Jackson Laboratory (Bar Harbor, ME, USA)and used in previous studies [21 (link)]. The AD mice show neurodegenerative signs at the age of 6 months and older. In this study, mice at 2 and 9 months old were used. Mouse memory was tested in Morris water maze. Aß plaques in mouse brain were analyzed using histochemistry. Mouse serum and brain lysates were examined using SDS-PAGE with immunoblotting. All animal procedures in this study were approved by the Institutional Animal Care and Use Committee in Taipei Medical University (LAC-2019–0448).
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2

Alzheimer's Disease Mouse Model Protocol

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The triple transgenic AD model mice (3 × Tg-AD) carrying human gene mutants APPswe, PS1M146V, and tauP301L were purchased from the Jackson laboratory (Bar Harbor, ME, USA). Six male 3 ×Tg AD mice were selected for the experiments of MOST technology, among them three were 6-month-old (abbreviated as AD06) and another three were 12-month-old (AD12).
All the animals were housed in an environment with a temperature of 22  ± 1 °C, relative humidity of 50  ± 1% and a light/dark cycle of 12/12 hr. Additionally, all animal studies (including the mice euthanasia procedure) were done in compliance with the regulations and guidelines of Shenzhen University Institutional Animal Care Center, Experimental Animal Ethics Committee of Shenzhen University Medical Department and the AAALAC and the IACUC guidelines (animal experiment proof certificate number: SYXK2014-0140).
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3

Loganin Treatment in 3xTg-AD Mice

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The 3xTg-AD mice harboring three mutant alleles (APPSwe, PS1M146V, and TauP301L) were purchased from Jackson Laboratory and kept in animals room of Shenzhen Center for Disease Control and Prevention (SZCDC). All animals were maintained specific conditions (temperature: 22 ± 2° C, relative humidity: 55 ± 15%) with free access to feed and water. In our experiment, the 7-month-old female mice were divided into three groups, and each group contained 10 to 15 mice. The 3xTg-AD mice were administrated daily with loganin (20 mg/kg body weight) for duration of 6 weeks. To avoid possible deviation to mice from long-term intraperitoneal injection, the control mice were injected with saline solution. Animal’s body weight was monitored every 3 days. After loganin treatment, mice were given to behavioral tests and then sacrificed for biochemical analysis. All animal care and experimental procedures were approved by the Ethics Committee of SZCDC. Every effort was made to alleviate animal’s suffering and minimize the number of mice used.
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4

Alzheimer's Disease Mouse Model Characterization

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1–42, Aβ1–42NT, Aβ1–42DM, Aβ1–42I, Aβ1–42Cl, and Aβ1–42NF (>95%, lyophilized powder) are synthesized by China Peptides (Shanghai, China). Thioflavin T (ThT), 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid (Bis-ANS) are obtained from Sigma–Aldrich (St. Louis, MO, USA). All other reagents are in the analytical grade. The female triple transgenic model mice of AD carrying human gene mutants APPswe, PS1M146V, and tauP301L are purchased from the Jackson Laboratory (Bar Harbor, ME, USA).
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5

Evaluating L-norvaline Effects on Alzheimer's Pathology

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Homozygous triple-transgenic mice (3×Tg-AD) harboring PS1(M146V), APP(Swe), and tau(P301L) transgenes were purchased from Jackson Laboratory (Bar Harbor, ME, USA) and bred in our animal facility. The 3×Tg-AD mice exhibited a synaptic dysfunction, plaque, and tangle pathology [84 (link)]. Four-month-old male 3×Tg-AD mice and age-matched male C57Bl/6 mice were divided randomly into four equal (20 mice each) groups according to their strain. The animals were housed in separate cages (five animals each) in constant ambient conditions and provided with water and food ad libitum. L-norvaline (Sigma) was dissolved in the animals’ drinking water (250 mg/L) and supplied in the animals’ cages for ten weeks in accordance with the previously published protocol [27 (link)]. The Bar-Ilan University animal care and use committee approved the experimental protocol (approval No. 82-10-2017) on October 1, 2017.
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6

Sacubitrilat Reduces Carbon Tetrachloride Toxicity

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Carbon tetrachloride (CCl4, Sigma, Deisenhofen, Germany) was diluted in corn oil (Sigma). Female and male 3xTg‐AD mice harboring PS1M146V, APPSwe, and tauP301L transgenes[72
] (Jackson Laboratories) and their WT controls (C57BL/6J) were injected intraperitoneally with 50 µL CCl4 in a final dose of 0,7 µL g−1 body weight twice a week (n = 12 per group). Control BL/6 animals were injected with the solvent (corn oil) only. Two groups of BL/6 mice (n = 8) received either 5 or 30 mg kg−1 body weight sacubitrilat (LBQ657, Hoelzel Diagnostika GmBH, Germany), injected daily over the entire period of 5‐week CCl4 treatment. All animals were euthanized under CO2 anesthesia. Blood was obtained by cardiac puncture and centrifuged after 30 min with 4.000 g at 4 °C for 10 min. Blood plasma and tissue samples were frozen at −80 °C until use.
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7

Norvaline Treatment in Transgenic Alzheimer's Mice

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Homozygous 3 × Tg mice, harboring PS1(M146V), APP(Swe), and tau(P301L) transgenes were purchased from Jackson Laboratory (Bar Harbor, ME, USA) and bred in our animal facility. These mice exhibit memory deficits associated with amyloid plaques deposition and tangle pathology [105 (link)].
Randomly chosen, male 4-month-old transgenic mice and age-matched male C57Bl/6 mice (wild-type) were divided into four groups (14 mice in each group) and housed in individually ventilated cages (Lab Products Inc., Seaford, DE, USA), with five mice per cage. The animals were provided with water and food ad libitum. The control animals received regular water. The experimental mice received water with dissolved (250 mg/L) norvaline (Sigma, St. Louis, MO, USA) for ten weeks in accordance with the previously published protocol [16 (link)]. The experiment lasted 2.5 months. The experiments were performed according to the “Guide for the Care and Use of Laboratory Animals” [106 (link)] and the experimental protocol (No 55-07-2018) was approved by Bar-Ilan University animal care and use committee.
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8

Transgenic Alzheimer's Mouse Model

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All procedures were approved by the Rockefeller University Institutional Animal Care and Use Committee. All mice were housed with a 12-hour light/12-hour dark cycle and fed ad libitum. Transgenic mouse lines (2xTg: APPswe/PSEN1dE9; 1xTg: Tg2576 harboring HuAPP695.KM670/671NL; 3xTg: PS1M146V, APPswe and tauP301L], and C57BL/6J WT mice were obtained from The Jackson Laboratory (Bar Harbor, ME, USA). Mice were anesthetized via Nembutal IP injection (50-100 µl) and intracardiac perfusion was performed first with 20 ml ice cold PBS then 20 ml ice cold PBS with 4% paraformaldehyde. Dissected cerebral tissue was post-fixed overnight in PBS with 4% PFA at 4°C followed by 1 hour at room temperature.
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9

Alzheimer's Mouse Model Characterization

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A total of 63 amyloid precursor protein (APP)/presenilin1 (PS1)/tau female mice (eight months old) containing three gene mutations (PS1M146V, APPSwe and tauP301L), were obtained from Jackson Laboratory (Bar Harbor, USA). Totally, 21 wild-type (WT) female mice (eight months old) with the same genetic background (C57BL/6J) purchased from the Animal Research Center of Shanxi Medical University were used as control mice. Compared with APP/PS1/tau male mice, female mice showed more progressed pathological characteristics in the brain and cognitive behavior impairments. Therefore, to reduce the difference caused by sex on pathological characteristics and cognitive behavior, APP/PS1/tau female mice were selected in our study. Mice were kept in an independent air supply system with a 12 h/ 12 h light-dark cycle at 23±2°C and 55%±5% humidity and supplied with standard food and water. All animal experimental procedures were approved by the Institutional Animal Care Committee of Shanxi Medical University.
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10

Norvaline Therapy in Transgenic AD Mice

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Homozygous triple-transgenic mice (3×Tg-AD) harboring PS1(M146V), APP(Swe), and tau(P301L) transgenes were purchased from Jackson Laboratory (Bar Harbor, ME, USA) and bred in our animal facility. These animals exhibit a synaptic deficiency, plaque, and tangle pathology (Oddo et al., 2003).
Male 4-month-old homozygous 3×Tg-AD mice weighing about 30 g were randomly divided into two groups (13 mice in each group). The animals were housed in cages (5 mice per cage) and provided with water and food ad libitum. The control animals received regular water. The experimental mice received water with dissolved L-norvaline (Sigma, St. Louis, MO, USA) (250 mg/L). The experiment lasted 2.5 months. The Bar-Ilan University Animal Care and Use Committee approved the experimental protocol (approval No. 82-10-2017) on October 1, 2017. The research was done in accordance with the “Guide for the Care and Use of Laboratory Animals” developed by National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals and “The Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research” developed by National Research Council (US) Committee on Guidelines for the Use of Animals in Neuroscience and Behavioral Research.
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