APOE Genotype Results in Differential Effects on the Peripheral Clearance of Amyloid-β42 in APOE Knock-in and Knock-out Mice
Matthew J. SharmanMichael MoriciEugene HoneTamar BergerKevin TaddeiIan MartinsWei Ling Florence LimSajla SinghMarkus R. WenkJorge GhisoJoseph D. BuxbaumSam GandyRalph N. Martins
52
Citation
19
Reference
10
Related Paper
Citation Trend
Abstract:
The ε4 allele of apolipoprotein E (APOE) is currently the major genetic risk factor identified for Alzheimer's disease (AD). Previous in vivo data from our laboratory has demonstrated that amyloid-β (Aβ) is rapidly removed from the plasma by the liveKeywords:
Apolipoprotein E
Gene knockin
Knockout mouse
Amyloid (mycology)
Apolipoprotein E
Knockout mouse
Neuropathology
Extravasation
Cite
Citations (75)
Knockout mouse
Gene knockin
Forebrain
Monoamine oxidase A
Gene knockout
Cite
Citations (0)
s of the First Congress of the Behavioral Pharmacology Society and the European Behavioural Pharmacology Society: PDF Only
Knockout mouse
Gene knockin
Cite
Citations (0)
Objective To oberseve the serum lipid and histopathology in ApoE gene knockout mice. Methods 24 ApoE gene knockout mice(bisexual each half) were selected,using 24 C57BL/6J mice as controls,to oberseve TC,LDL,HDL and the change of heart pathological morphology. Results The TC,LDL level of ApoE gene knockout mice were significantly higher than in control groups(P 0.05);the HDL level had no significantly difference in both groups;the area of atherosclerotic plaque of ApoE gene knockout mice was significantly higher than in control groups(P 0.05);there was clinical occurrence of atherosclerosisin ApoE gene knockout mice. Conclusion ApoE gene knockout mice promotes atherosclerosis easily.
Apolipoprotein E
Knockout mouse
Histopathology
Gene knockout
Cite
Citations (0)
Gene knockin
Knockout mouse
Cite
Citations (0)
Abstract Background Apolipoprotein E (APOE) and clusterin (CLU) are critical in the pathogenesis of Alzheimer’s disease (AD). Common coding variants in APOE (e.g. APOE4) impart at least 3‐fold higher risk of developing AD, while common noncoding variants in CLU impart smaller but still highly significant risk for AD. Using genetically engineered mouse models lacking either APOE or CLU, previous studies from our lab and others have shown that both are critical in the formation of amyloid. However, only a single published study has examined the combined effects of APOE and CLU in a mouse model of amyloidosis. Methods We generated mice that lacked both murine APOE and CLU (double knockout mice) on the APP/PS1 background of AD amyloidosis. We assessed these mice using histological analysis as well as single‐cell RNAseq profiling from brain tissue. Results Compared to APP/PS1 controls, we found that double knockout mice for both APOE and CLU had a striking reduction in the amount of amyloid plaques in the cortex. Moreover, we found that these double‐knockout mice were completely void of amyloid plaques in the hippocampus. Single‐cell RNAseq experiments revealed a strong reduction in the amount of activated microglia in these double knockout mice. Conclusions Contrary to a previous study that reported increased amyloid load in APOE‐/‐;CLU‐/‐ double knockout mice, we found a dramatic reduction in amyloid plaques and a concomitant loss of activated microglia when using genetically inbred (C57BL/6J) mouse lines. Further studies are needed to determine whether these effects are cell‐type specific (e.g. astrocyte‐derived APOE and CLU conditional knockouts) or whether these lipoproteins have synergistic roles in tau pathology.
Apolipoprotein E
Knockout mouse
Clusterin
Amyloid (mycology)
Gene knockin
BACE1-AS
Pathogenesis
Cite
Citations (0)
PurposeTo study the morphologic characteristics of the optic nerve (ON) by using an experimental model of knockout mice for expression of the ApoE geneMethodsEyeballs with the retrobulbar ON attached were obtained from 24-week-old mice. Using morphologic and morphometric techniques and light and transmission electron microscopy, the ON characteristics were determined in three groups of mice: 1) wild type mice as the controls (CG; n=15), 2) knockout mice for the ApoE gene (ApoE-G; n=15), and 3) knockout mice for the ApoE gene that were fed a cholesterol-supplemented diet (ApoED-G; n=15).ResultsThe ON cross-sectional area was significantly higher in the ApoE-G than in the CG (p<0.001) mice, whereas no significant changes were noticed between the ApoE-G and ApoED-G mice. Significant differences were noticed between those groups regarding the myelination index. Higher density of intraaxonal degeneration and myelin sheath alterations were found in both ApoE groups in respect to the CG.ConclusionsThese results suggest that ApoE knockout mice have changes in ON morphology and myelination.
Apolipoprotein E
Knockout mouse
Ratón
Cite
Citations (8)
The ε4 allele of apolipoprotein E (APOE) is currently the major genetic risk factor identified for Alzheimer's disease (AD). Previous in vivo data from our laboratory has demonstrated that amyloid-β (Aβ) is rapidly removed from the plasma by the live
Apolipoprotein E
Gene knockin
Knockout mouse
Amyloid (mycology)
Cite
Citations (52)
Gene knockin
Knockout mouse
Gene knockout
Cite
Citations (1)
ApoE is an important component of plasma lipoproteins,and plays significant roles in lipoprotein metabolism.The absence or mutation of apoE may give rise to abnormal metabolism in vivo and dysfunction of organs,and then lead to a series of diseases and complications.Since the generation of apoE knockout mice,they have offered a wonderful base to study the functions of apoE and its roles in various related disease.Recently,the apoE knockout mice have been regarded as one of most popular animal models in experimental atherosclerosis research.
Apolipoprotein E
Knockout mouse
Cite
Citations (0)