Aav8-pcsk9 Mice
Aav8-pcsk9 Mice - Related Videos
08:14
A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
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Cited by 1 •
2018
This protocol presents a method to evaluate the proteolytic activity of an intrinsically low-activity, single turnover protease in a cellular context. Specifically, this method is applied to evaluate the proteolytic activity of PCSK9, a key driver of lipid metabolism whose proteolytic activity is required for its ultimate hypercholesterolemic function.
04:29
Efficient Gene Knockdown in the Liver via Intrasplenic Injection of Adeno-Associated Virus Serotype 8 (AAV8)-Delivered Small Hairpin RNA
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2024
This protocol describes how intrasplenic injection of AAV8-delivered small hairpin RNA achieves the same gene knockdown efficiency in the liver as portal vein injection, representing a simpler procedure with much lower perioperative and postoperative mortality and complications.
06:17
Measuring the Strength of Mice
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Cited by 287 •
2013
Deficits in muscular strength occur in many clinical conditions such as motor neuron disease. The inverted screen and weight lifting tests described here measure strength in mice almost exclusively, with minimal influence of factors such as coordination.
36:30
Small Bowel Transplantation In Mice
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Cited by 2 •
2007
The mouse small bowel transplantation model has been recognized as an important tool to study mechanismes of immune rejection and screen new immunosuppressive drugs. However, this model is limited to use because the techniques involved is an extremely technically challenge. Now we introduce the modified technique.
07:02
Trace Fear Conditioning in Mice
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Cited by 32 •
2014
In the following experiment we describe a protocol for trace fear conditioning in mice. This type of associative memory includes a trace period that separates the neutral stimulus and the unconditioned stimulus.
FAQs
Increased hepatic PCSK9 binds LDL receptors and directs them toward lysosomal degradation. With fewer receptors available, the liver clears less LDL from the bloodstream, producing elevated cholesterol. This receptor-level mechanism connects the viral model to lipid metabolism and provides a defined biological basis for testing interventions that aim to restore or preserve LDL clearance.
Sustained production maintains the cholesterol-altering stimulus after AAV8 delivery rather than creating only a brief exposure. That persistence helps establish a stable acquired hypercholesterolemic state and supports investigations of disease mechanisms or treatments over time. The resulting condition is also relevant to studying how prolonged lipid abnormalities contribute to atherosclerosis-prone biology.
The model produces the phenotype through systemic delivery of a PCSK9-expressing virus rather than through a germline genetic modification. This distinction allows researchers to create acquired hypercholesterolemia in otherwise non-germline-modified animals. It therefore offers a practical alternative for examining cholesterol-related biology and therapeutic responses without establishing a heritable mutation.
The pathway links a molecular event in the liver with a measurable change in circulating LDL and a condition prone to atherosclerosis. That connection makes the mice useful for examining how altered lipid metabolism may influence vascular disease. It also provides a mechanistic framework for interpreting whether an intervention changes cholesterol handling or downstream disease-related outcomes.
Generation begins with systemic administration of an AAV8 vector carrying a PCSK9 expression program. The vector promotes hepatic PCSK9 production, after which LDL receptor degradation reduces LDL clearance and cholesterol rises. This workflow rapidly establishes the acquired hypercholesterolemic state used for subsequent biological measurements or intervention studies.
The model supports evaluation of cholesterol-lowering drugs, gene therapies, and dietary effects. Researchers can use the induced lipid disturbance to examine whether these interventions alter the hypercholesterolemic state or its atherosclerosis-prone consequences. Because the initiating mechanism is defined through PCSK9 and LDL receptor handling, treatment responses can also be interpreted in a lipid-metabolism context.
These mice connect liver-directed molecular biology with systemic lipid and vascular phenotypes. Their applications include studying lipid metabolism, investigating mechanisms associated with cardiovascular disease, and testing therapeutic strategies. The model is especially useful when researchers need a rapidly established, acquired cholesterol abnormality to examine biological responses without relying on germline genetic modification.