What are ApoE knockout mice?
These ApoE KO mice are useful for studying cardiovascular disease, atherosclerosis and fat metabolism, as well as the role of ApoE in Alzheimer’s disease.
What are LDLR -/- mice?
1 LDLR−/− Mice. The LDLR−/− mice (low-density lipoprotein, LDL, receptor) are the models for studying familial hypocholestrolemia. These mice have a mutation that affects the LDLR; therefore, they resemble humans in the plasma lipoprotein profile.
Why are ApoE mice used?
Apoe−/− mice are a particularly useful strain to investigate comorbidities associated with cigarette smoking because, together with premature atherosclerosis [10], they show impaired alveologenesis [40] and develop emphysema [20, 41] (Fig.
Which human disease is mimicked by the mouse LDL receptor knockout mouse?
One of the commonly used models for atherosclerosis studies is the low density lipoprotein (LDL) receptor knock-out (Ldlr−/−) mouse. The LDL receptor plays a major role in the clearance of apoB and apoE-containing lipoproteins [9].
How does APOE cause Alzheimer’s?
ApoE, present in the CNS and the periphery, represents a critical link between these two compartments and could influence Alzheimer’s disease (AD) pathogenesis by disrupting the blood–brain barrier (BBB) integrity from both sides (Chernick et al., 2019).
How do you induce atherosclerosis in mice?
Lipid-enriched diets are often used to induce or accelerate the rate of atherosclerotic lesion development in murine models of atherosclerosis. It appears that the induction of persistent hypercholesterolemia to levels >&300 mg/dL is required for the development of experimental atherosclerosis in the mouse.
Do mice have LDL?
For example, they lack cholesteryl ester transfer protein (CETP),21 which shuttles cholesteryl esters from HDL to apoB-containing lipoproteins such as LDL and very low density lipoproteins (VLDL) in humans. Thus, mice carry the majority of plasma cholesterol in HDL22 while humans carry much of it in LDL.
What is a foam cell?
Definition. Foam cells are a type of macrophage that localize to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance.
What does APOE do in the brain?
As the major component of HDL-like particles in the brain, ApoE facilitates the transfer of cholesterol and phospholipid between cells. ApoE serves as a ligand in the receptor-mediated endocytosis of HDL-like particles through LDL receptor family. There are three major isoforms (ApoE2, ApoE3, and ApoE4) in humans.
What Does the APOE 4 gene Do?
The reason APOE4 increases Alzheimer’s risk is not well understood. The APOE protein helps carry cholesterol and other types of fat in the bloodstream. Recent studies suggest that problems with brain cells’ ability to process fats, or lipids, may play a key role in Alzheimer’s and related diseases.
How is atherosclerosis measured in mice?
There are a number of methods for the quantification of atherosclerosis in mice and the three vascular beds most commonly analysed are: (i) the aortic root and ascending aorta cut in cross-section (ii) the aortic tree spanning the arch, thoracic and abdominal regions of the aorta opened longitudinally to expose the …
What animals get atherosclerosis?
Is atherosclerosis a disease affecting all animals or only certain animals? Atherosclerosis affects only herbivores. Dogs, cats, tigers, and lions can be saturated with fat and cholesterol, and atherosclerotic plaques do not develop (1, 2).
How does cholesterol metabolism differ between humans and rats?
Research Articles. Of mice and men: murine bile acids explain species differences in the regulation of bile acid and cholesterol metabolism[S] Compared with humans, rodents have higher synthesis of cholesterol and bile acids (BAs) and faster clearance and lower levels of serum LDL-cholesterol.
Are foam cells good?
Foam cells form the fatty streaks of the plaques of atheroma in the tunica intima of arteries. Foam cells are not dangerous as such, but can become a problem when they accumulate at particular foci thus creating a necrotic centre of atherosclerosis.
Where do foam cells come from?
Foam cells are a type of macrophage that localize to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance.
Where is APOE produced?
ApoE is produced in abundance in the brain and serves as the principal lipid transport vehicle in CSF. It is induced at high concentration in peripheral nerve injury and appears to play a key role in repair by redistributing lipids to regenerating axons and to Schwann cells during remyelination.
Why does APOE cause Alzheimer’s?
How common is APOE e4?
About 25% of people carry one copy of APOE4, and 2 to 3% carry two copies. APOE4 is the strongest risk factor gene for Alzheimer’s disease, although inheriting APOE4 does not mean a person will definitely develop the disease.
Do mice get atherosclerosis?
Unlike humans, mice seldom develop atherosclerosis in the coronary arteries, but readily develop atherosclerosis in the aortic root. The much more rapid heart rate of the mouse and hence disturbed blood flow probably accounts for the atherosclerosis predilection at this site.
What is the pathophysiology of LDLR knockout mice?
LDLr knockout mice also develop hypercholesterolemia through inhibition of the removal of circulatory LDL. Fed a high-cholesterol diet, LDLr knockout mice develop extreme hyperlipidemia and hyperglycemia, characteristics of the metabolic syndrome.
Why are LDLR mice preferred for APOE-sufficient donors?
Further, in experiments involving bone marrow transplantation, Ldlr mice are the preferred model because bone marrow from Apoe -sufficient donors can reduce the atherosclerotic phenotype of Apoe -deficient hosts. But wait! There’s more!
How does aging affect cholinergic neurons in APOE KO mice?
Behavioral and LTP studies show that ApoE KO mice do not exhibit any difference from control mice. Since the cholinergic system is severely affected in AD, the effects of aging on the integrity of this system were investigated, finding that the number and size of cholinergic neurons was not affected in Apo EKO mice ( Fagan et al., 1998 ).
Do ApoE-deficient mice develop atherosclerosis more similar to humans?
With respect to atherosclerotic plaque development, Apoe -deficient mice develop progressive lesions more characteristic of those observed in humans. The lipid profile of Ldlr -deficient mice – with a higher percentage of cholesterol carried in IDL/LDL particles– more closely resembles that in dyslipidemic humans, however.