The DOI matches its Crossref record; 31 of the 33 references it cites were found in a registry or an index; none of the 27 sources its claims cite is checked for support yet.
Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2.
Open accessAbstract
To study isoform-specific effects of apolipoprotein E (apoE) in vivo, we generated mice with a human APOE*2 allele in place of the mouse Apoe gene via targeted gene replacement in embryonic stem cells. Mice expressing human apoE2 (2/2) have virtually all the characteristics of type III hyperlipoproteinemia. Their plasma cholesterol and triglyceride levels are both twice to three times those in (normolipidemic) mice that are expressing human apoE3 (3/3) made in an identical manner. The 2/2 mice are markedly defective in clearing beta-migrating VLDL particles, and spontaneously develop atherosclerotic plaques, even on a regular diet. An atherogenic diet, high in fat and cholesterol, exacerbates development of atherosclerosis and xanthomas in the 2/2 mice. Thus, comparisons between the 2/2 and 3/3 mice unequivocally demonstrate that a single amino acid difference (Arg158 Cys) in the apoE protein is sufficient to cause type III HLP and spontaneous atherosclerosis in mice.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Targeted replacement of the mouse Apoe gene with human APOE*2 produced mice with virtually all features of type III hyperlipoproteinemia and spontaneous atherosclerosis, whereas mice carrying human APOE*3 made identically were normolipidemic. The paper concludes that a single amino acid difference (Arg158→Cys) in apoE is sufficient to cause type III HLP and spontaneous atherosclerosis in mice.
Key findings
- APOE*2 homozygous (2/2) mice had plasma total cholesterol and triglycerides two to three times higher than APOE*3 homozygous (3/3) mice on normal chow; e.g., females: TC 238 ± 48 vs. 75 ± 15 mg/dl and TG 184 ± 46 vs. 48 ± 13 mg/dl (P < 0.0001). HDL cholesterol did not differ, and 2/3 heterozygotes had normal lipid levels.
- 2/2 mice showed β-VLDL accumulation: broad β-migration on agarose gels, VLDL cholesterol-to-triglyceride ratio 0.76 vs. 0.03 in 3/3 mice, and ~65% of total cholesterol in VLDL-IDL fractions vs. >85% in HDL for 3/3 mice. Plasma apoE2 was 16-fold higher than apoE3 in 3/3 mice.
- Clearance of radiolabeled apoE-deficient remnant particles was severely delayed in 2/2 mice: fractional catabolic rate 0.007/min vs. 0.02/min in 3/3 mice, with ~50% of label remaining at 2 h in 2/2 and apoE−/− mice.
- 2/2 mice spontaneously developed atherosclerosis on regular chow: all seven 10-month-old females evaluated had plaques near the aortic root, average size 9.4 × 10^4 (as reported; text labels area units m²), vs. smaller plaques in 4 of 11 3/3 females, average 1 × 10^3. An atherogenic diet enhanced plaque size in 2/2 females to 5.3 × 10^5, eight times larger than 3/3 females (6.4 × 10^4), and caused xanthomas.
Methods
- Gene replacement in mouse embryonic stem cells replaced the mouse Apoe gene with human APOE*2, using the same strategy previously used for APOE*3; mice were 129/C57BL/6 F2 hybrids, with 2/3 heterozygotes from F3 matings.
- Mice were fed regular chow, an atherogenic diet (15.8% fat, 1.25% cholesterol, 0.5% sodium cholate), or a western-style diet (21% fat, 0.2% cholesterol). Plasma lipids, lipoproteins, apoE, and apoB were analyzed by enzymatic assays, agarose gel electrophoresis, FPLC, SDS-PAGE, and ELISA.
- Remnant clearance was measured after injection of 14C-labeled β-VLDL from apoE−/− mice into 2/2, 3/3, and apoE−/− mice; atherosclerosis was assessed histologically in proximal aorta/aortic sinus sections. Statistical comparisons used two-tailed unpaired Student t tests or Mann-Whitney U tests.
Limitations
- The paper has no explicit limitations section. It states that one of four 2/2 mice did not respond to clofibrate and the reason is unknown, possibly related to its F2 genetic background.
- The authors state that mechanisms for different triglyceride and HDL responses to the western vs. atherogenic diets are unknown, though they attribute the differences most likely to diets rather than sex.
- Evident from the text: the model may overstate human relevance because mice synthesize ~70% of liver-derived VLDL as apoB48 particles and depend more on apoE for VLDL remnant clearance than humans, so the apoE2 vs. apoE3 difference has a larger impact in mice than in most humans.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 27 cited sources checked · 0 supported · 0 flagged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Their plasma cholesterol and triglyceride levels are both twice to three times those in (normolipidemic) mice that are expressing human apoE3 (3/3) made in an identical manner.”
- Also stated in: § Results · plain
“plasma TC and TG levels in the 2/2 mice are two to three times higher than those in the 3/3 mice, which are themselves normolipidemic (Table I, P Ͻ 0.0001).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An atherogenic diet, high in fat and cholesterol, exacerbates development of atherosclerosis and xanthomas in the 2/2 mice.”
- Also stated in: § Delayed clearance of VLDL and spontaneous atherosclerosis. · plain
“Thus, a diet high in fat and cholesterol exacerbates the hyperlipidemia as well as development of atherosclerosis in the 2/2 animals.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § Delayed clearance of VLDL and spontaneous atherosclerosis. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 2/2 mice are markedly defective in clearing  -migrating VLDL particles”
- Also stated in: § Discussion · boosted
“These results show that the 2/2 mice have a severe defect in clearing larger lipoproteins”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Discussion · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, the lesions in the 3/3 mice consisted solely of foam cells (Fig. 3 C).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Strength:plain· not yet calibratedn = 3Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the three animals that responded, mean plasma TG levels decreased from elevated (188 mg/dl) to normal levels (61 mg/dl, P Ͻ 0.001).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Isoelectric focusing of whole plasma from mice homozygous for APOE*2 (2/2), heterozygous for APOE*2 and ApoE*3 (2/3), and homozygous for APOE*3 (3/3) shows that the mice are producing human apoE2 and apoE3 isoforms indistinguishable from those present in human plasma (Fig. 1 A ).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, unlike humans in which apoE2 homozygosity is necessary but not sufficient to cause type III HLP, all the 2/2 mice, regardless of gender and age, develop hyperlipidemia, even on a low-fat and low-cholesterol diet.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Lipid-laden macrophages were abundantly present in other tissues such as the fa-cial plane of skeletal muscle, submucosa of the esophagus, and the lymph nodes.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Strength:plain· not yet calibratedn = 2Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Histological examination of the skin showed numerous foam cells, cholesterol clefts, and neutrophils in the hypodermis (Fig. 3 D).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Strength:plain· not yet calibratedn = 2Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The lipoproteins in the HDL range were larger as judged by a shift in the HDL cholesterol peak.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- The quote only partly states this claim. 3
- It may state two separate claims as one. 27
- Probably not a substantial claim. 10
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and spontaneously develop atherosclerotic plaques, even on a regular diet.”
- Also stated in: § Delayed clearance of VLDL and spontaneous atherosclerosis. · plain
“we found atherosclerotic plaques in the proximal aorta of 10-mo-old female 2/2 mice maintained on regular chow.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
- Also stated in: § Delayed clearance of VLDL and spontaneous atherosclerosis. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accumulation of  -VLDL in 2/2 plasma is further illustrated by fast protein liquid chromatography (FPLC), which shows that ف 65% of the total cholesterol is in lipoproteins that elute in the VLDL-intermediate density lipoprotein (IDL) range (fractions 15-23, Fig. 1 C ); in contrast, Ͼ 85% of the cholesterol in the 3/3 mice is in the HDL range (fractions 27-31).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Feeding the atherogenic diet for 3 mo enhanced plaque development in the female 2/2 mice (mean size, 5.3 ϫ 10 5 m 2 , n ϭ 9); and the plaques were eight times larger than those found in the 3/3 female mice (6.4 ϫ 10 4 m 2 , n ϭ 6) on the same diet.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Animals of both sexes are equally affected, and plasma lipid levels are elevated at 2 mo of age and remain stable for over 1 yr.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The livers of 2/2 mice on the atherogenic diet, however, appeared relatively normal on gross examination, while the wild-type livers were enlarged and pale.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All seven 2/2 females evaluated had plaques near the aortic root, with a cross-sectional area ranging from 2 ϫ 10 4 to 2 ϫ 10 5 m 2 (average size, 9.4 ϫ 10 4 m 2 ).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both whole plasma and the d Ͻ 1.006 g/ml density fraction of plasma from 2/2 mice show this broad  -migration pattern (Fig. 1 B ); in contrast, 3/3 plasma shows virtually no lipid staining at the  -position.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On an atherogenic diet that contains 15.8% fat, 1.25% cholesterol, and 0.5% sodium cholate, female 2/2 mice responded with a fivefold increase in plasma TC (P Ͻ 0.001), while their TG and HDL cholesterol levels were significantly reduced (P Ͻ 0.001, Table I).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The amount of apoB100 in the LDL fraction of 2/2 mice was similar to that in the 3/3 mice (data not shown).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
Strength:plain· not yet calibratedn = 2Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fig. 3 A shows a representative section with plaques composed mainly of foam cells and some fibrous caps.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Strength:plain· not yet calibratedn = 2Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ApoB48 was increased equally in both VLDL and IDL-LDL fractions, while the increase in apoB100 was mainly in the VLDL fraction.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The majority of TG in both groups of mice is in the VLDL fraction, although the TG levels in the 2/2 mice are much higher than in the 3/3 mice.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, very much smaller plaques (average size, 1 ϫ 10 3 m 2 ), typically an accumulation of several foam cells, were found in only 4 of 11 female 3/3 mice aged 10-12”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the lesions in the 2/2 mice consisted chiefly of foam cells, many also had fibrous caps, cholesterol clefts, and necrotic cores (Fig. 3 B).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In marked contrast, the hepatocytes in the wild-type livers were enlarged with microvesicular lipid deposits, and the numbers of anucleate and binucleate hepatocytes were increased (Fig. 3 F).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SDS-PAGE also revealed that both the ApoB100 and apoB48 amounts in 2/2 plasma were increased two-and eightfold, respectively, compared with the 3/3 mice.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ApoE2 was associated with lipoproteins in the VLDL-IDL range, and appeared as two distinct peaks (fractions 15 and 20) by FPLC analysis.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“FPLC analysis (Fig. 1 C ) showed a marked decrease in cholesterol and TG in the larger lipoproteins (VLDL-IDL range), while HDL cholesterol was increased.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When male 2/2 mice were placed on a western-style diet containing 21% fat and 0.2% cholesterol, their plasma TC levels tripled (P Ͻ 0.001), accompanied by a slight but not statistically significant increase in TG, and no change in HDL cholesterol (Table I).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Type III hyperlipoproteinemia (HLP) 1 is characterized by accumulation of chylomicron and VLDL remnants, collectively termed  -VLDL, which results in elevated plasma levels of total cholesterol (TC) and triglycerides (TG).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Introduction
What the sources say
- Not matchedcites [1]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Mice consequently depend more on apoE for VLDL remnant clearance than do humans, in whom all the VLDL particles from the liver contain apoB100 and can be cleared via the LDL receptor independently of apoE.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Discussion
What the sources say
- Not matchedcites [23]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, a diet high in fat and cholesterol exacerbates the hyperlipidemia as well as development of atherosclerosis in the 2/2 animals.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These changes and their differences between the 2/2 and the 3/3 mice suggest that the apoE2 is an ineffective ligand for removing lipoproteins via hepatocellular lipoprotein receptors, thereby protecting hepatocytes from fatty changes while accelerating lipoprotein uptake by a default pathway that likely involves macrophages and Kupffer cells.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“The differences between the apoE2 and apoE3 isoforms have a much larger impact in mice than in most humans, possibly because mice synthesize ف 70% of their liver-derived VLDL as apoB48 particles (23,24).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Discussion
What the sources say
- Not matchedcites [23]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
In the paper
“Diets high in fat and cholesterol exacerbate the hyperlipoproteinemia found in the 2/2 animals, in agreement with the inverse observation that changing to a low-fat, lowcholesterol diet alleviates the hyperlipidemia in most human type III HLP patients (1).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Discussion
What the sources say
- Not matchedcites [1]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Not matched
In the paper
“The majority of apoE2 homozygotes have below average plasma cholesterol levels, but 5-10% of homozygotes develop type III HLP.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Introduction
What the sources say
- Not matchedcites [3]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“Thus, additional genetic, hormonal, or environmental factors are required to precipitate the disease (3).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Introduction
What the sources say
- Not matchedcites [3]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Not matched
In the paper
“For example, transgenic mice expressing low levels of human apoE2 are hypolipidemic, while those expressing high levels are hyperlipidemic (7).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Introduction
What the sources say
- Not matchedcites [7]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“These animals have some of the characteristics of type III HLP, but rigorous comparisons to other transgenic mice expressing the common human apoE3 isoform are not possible because the transgenes were inserted into the genome in different copy numbers and in different chromosomal locations.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Introduction
What the sources say
- Not matchedcites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
In the paper
“(a ratio Ͼ 0.3 is diagnostic for type III HLP in humans [15]).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
What the sources say
- Not matchedcites [15]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Another distinguishing characteristic of patients with type III HLP is the presence of planar and dermal xanthomas (20,21).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Delayed clearance of VLDL and spontaneous atherosclerosis.
What the sources say
- Not matchedcites [20]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [21]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“These alterations in plasma lipoprotein profiles after clofibrate treatment are again very similar to what has been observed in human patients treated with fibrates (19).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Distribution of lipids and lipoproteins.
What the sources say
- Not matchedcites [19]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Additionally, the presence of endogenous mouse apoE protein in some cases complicates the interpretation of the phenotype.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Introduction
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“We have previously reported the use of a gene replacement strategy to generate mice with a human APOE*3 allele in place of the mouse Apoe gene, and have demonstrated that these mice express human apoE3 transcripts in a tissue-specific and physiological manner (10).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Introduction
What the sources say
- Not matchedcites [10]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is reasonable to expect that human apoE proteins would not be as good ligands to mouse receptor(s) as they are to human receptor(s), and further reduction of this interaction after the Arg-158→Cys substitution in the apoE2 protein is the likely cause of the hyperlipidemia seen in the 2/2 mice, even on the regular chow.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Reduced plasma lipoprotein clearance due to hormonal, dietary, and genetic changes that lower LDL receptor expression is thought to be a factor that triggers the type III HLP phenotype in human patients (1).”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Discussion
What the sources say
- Not matchedcites [1]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Not matched
In the paper
“Nevertheless, the 3/3 mice are more susceptible to diet-induced hyperlipidemia than are wild-type mice (10), suggesting that human apoE3 is still not as good of a ligand to mouse receptor(s) as mouse apoE protein.”
§ Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE * 2 > Discussion
What the sources say
- Not matchedcites [10]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
The paper relies on this without support.
The primary molecular cause of type III HLP is a dysfunctional form of apolipoprotein E.
“The primary molecular cause of the disease is the presence of a dysfunctional form of apolipoprotein (apo) E, a critical ligand needed for plasma lipoprotein clearance.”
The paper relies on this without support.
The majority of type III HLP individuals are homozygous for the apoE2 isoform.
“The majority of type III HLP individuals are homozygous for the apoE2 isoform, although in rare instances dominant apoE mutations are associated with the disease.”
The paper relies on this without support.
ApoE2 differs from apoE3 by a single amino acid substitution, cysteine at position 158 in place of arginine.
“ApoE2 differs from the most common isoform, apoE3, by only a single amino acid substitution, cysteine at position 158 in place of arginine.”
The paper relies on this without support.
Type III HLP is characterized by accumulation of chylomicron and VLDL remnants (beta-VLDL), resulting in elevated plasma TC and TG.
“Type III hyperlipoproteinemia (HLP) 1 is characterized by accumulation of chylomicron and VLDL remnants, collectively termed  -VLDL, which results in elevated plasma levels of total cholesterol (TC) and triglycerides (TG).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“APOE ε2-TR or APOE ε4-TR mice retain regulatory sequences of the mouse Apoe gene and the noncoding murine exon 1 surrounding the inserted human exons 2′, 3′, and 4′ [17,18] and therefore, they express the human apoE protein at physiological levels.”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [17]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“E2-TR mice display a plasma lipid profile similar to the type III hyperlipoproteinemia found in ~5–10% of E2/E2 humans, particularly when challenged with a high-fat diet (HFD)20.”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [20]
The cited source says what the claim attributes to it.
In the citing paper
“Because Sullivan et al.20 reported HLP-III-like plasma lipids in E2-TR mice”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as Sullivan et al.20
The cited source says what the claim attributes to it.
In the citing paper
“These findings are consistent with type III hyperlipoproteinemia, previously described in human APOE ε2-TR mice [17].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“APOE ε2 targeted replacement mice develop type III hyperlipoproteinemia and spontaneous atherosclerosis [16] as well as volume overload as a function of their obesity, all of which are recognized vascular risk factors and may explain increased preponderance to thalamic localization of hemosiderin deposits in APP/ε2 mice found in our study.”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“APOE ε2 targeted replacement mice develop type III hyperlipoproteinemia and spontaneous atherosclerosis [16] as well as volume overload as a function of their obesity, all of which are recognized vascular risk factors and may explain increased preponderance to thalamic localization of hemosiderin deposits in APP/ε2 mice found in our study.”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [16]
Citations
Cites
Goldstein, J. L., Ho, Y. K., Basu, S. K., & Brown, M. S. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.1.333 · Cited by 2,447
Plump, A. S., Smith, J. D., Hayek, T., Aalto-Setälä, K., Walsh, A., Verstuyft, J. G., Rubin, E. M., & Breslow, J. L. (1992) · Cell · doi:10.1016/0092-8674(92)90362-g · Cited by 2,263
Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein E
Zhang, S. H., Reddick, R. L., Piedrahita, J. A., & Maeda, N. (1992) · Science · doi:10.1126/science.1411543 · Cited by 2,237
Self-citationFat Transport in Lipoproteins — An Integrated Approach to Mechanisms and Disorders
Fredrickson, D. S., Levy, R. I., & Lees, R. S. (1967) · New England Journal of Medicine · doi:10.1056/nejm196701052760107 · Cited by 1,911
Henriksen, T., Mahoney, E. M., & Steinberg, D. H. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.10.6499 · Cited by 1,025
Weisgraber, K. H., Innerarity, T. L., & Mahley, R. W. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34954-8 · Cited by 673
Polymorphism of apolipoprotein E and occurrence of dysbetalipoproteinaemia in man
UTERMANN, G., HEES, M., & STEINMETZ, A. (1977) · Nature · doi:10.1038/269604a0 · Cited by 666
Sullivan, P. M., Mezdour, H., Aratani, Y., Knouff, C., Najib, J., Reddick, R. L., Quarfordt, S. H., & Maeda, N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.29.17972 · Cited by 575
Self-citationFat Transport in Lipoproteins — An Integrated Approach to Mechanisms and Disorders
Fredrickson, D. S., Levy, R. I., & Lees, R. S. (1967) · New England Journal of Medicine · doi:10.1056/nejm196701122760206 · Cited by 497
Synthetic low and high fat diets for the study of atherosclerosis in the mouse.
Nishina, P. M., Verstuyft, J. G., & Paigen, B. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42785-3 · Cited by 293
Flagged first, then by citations
2 of the 33 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–200 of 254
Microglial function in human APOE3 and APOE4 transgenic mice: altered arginine transport
Czapiga, M., & Colton, C. A. (2003) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00394-6 · Cited by 38
Altenburg, M. K., Arbonés-Mainar, J. M., Johnson, L. A., Wilder, J., & Maeda, N. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.164863 · Cited by 38
Self-citationAndrogen-Mediated Immune Function Is Altered by the Apolipoprotein E Gene
Brown, C. M., Xu, Q., Okhubo, N., Vitek, M. P., & Colton, C. A. (2007) · Endocrinology · doi:10.1210/en.2006-1200 · Cited by 38
Maezawa, I., Zaja‐Milatovic, S., Milatović, D., Stephen, C., Sokal, I., Maeda, N., Montine, T. J., & Montine, K. S. (2006) · Journal of Neuroinflammation · doi:10.1186/1742-2094-3-21 · Cited by 39
“Maeda and colleagues and are backcrossed greater than six generations to a C67Bl/6 genetic background [41,42].”
BackgroundSelf-citationAltenburg, M., Johnson, L., Wilder, J., & Maeda, N. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610712200 · Cited by 34
Self-citationNwabuisi‐Heath, E., Rebeck, G. W., LaDu, M. J., & Yu, C. (2013) · ASN NEURO · doi:10.1042/an20130043 · Cited by 38
“In the cortex of human APOE-targeted replacement (APOE-TR) mice (Sullivan et al., 1997, 1998) dendritic spine density and dendritic complexity was lowest in APOE4-TR mice, compared with APOE2- and APOE3-TR mice (Dumanis et al., 2009).”
BackgroundHoos, M. D., Vitek, M. P., Ridnour, L. A., Wilson, J. G., Jansen, M., Everhart, A. L., Wink, D. A., & Colton, C. A. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-50 · Cited by 38
“There are currently many examples of this type of approach including multiple models of neurodegenerative disease where a mutated gene is added in addition to the mouse gene (for example, the APPsw-Tg2576 mice; [36] or where the human gene replaces a large part of the mouse gene with or without replacing the promoter…”
BackgroundKnouff, C., Malloy, S., Wilder, J., Altenburg, M. K., & Maeda, N. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009423200 · Cited by 28
Self-citationRelevance of transgenic mouse models for Alzheimer's disease
Tai, L. M., Weng, J. M., LaDu, M. J., & Brady, S. T. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.07.007 · Cited by 39
ApoE isoform‐dependent deficits in extinction of contextual fear conditioning
Olsen, R. H. J., Agam, M., Davis, M. J., & Raber, J. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00833.x · Cited by 35
“Three to six-month-old Targeted Replacement (TR) apoE2 (Sullivan et al. 1998), apoE3 (Sullivan et al. 1997), and apoE4 (Knouff et al. 806 © 2012 The Authors Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society 1999) mice, expressing…”
BackgroundSharman, M. J., Shui, G., Fernandis, A. Z., Lim, W. L. F., Berger, T., Hone, E., Taddei, K., Martins, I. J., Ghiso, J., Buxbaum, J. D., et al. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-1348 · Cited by 35
“These mice have been previously described [20–23].”
Lim, W. L. F., Lam, S. M., Shui, G., Mondal, A., Ong, D., Duan, X., Creegan, R., Martins, I. J., Sharman, M. J., Taddei, K., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.03.012 · Cited by 37
“These mice have been described previously (Knouff et al., 1999; Piedrahita et al., 1992; Sullivan et al., 1997; Sullivan et al., 1998).”
Athanasopoulos, T. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.17.2545 · Cited by 35
“Of the three major isoforms, the rarest variant, apoE2, is associated with type III hyperlipoproteinaemia (4,5) and differs from wild-type apoE3 by an R158C substitution; apoE4 (C112R) produces a dominant hyperlipidaemia (6) and is implicated in re-stenosis (7).”
BackgroundPankiewicz, J. E., Baquero-Buitrago, J., Sanchez, S., Lopez-Contreras, J., Kim, J., Sullivan, P. M., Holtzman, D. M., & Sadowski, M. J. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0156-1 · Cited by 34
“In view of these considerations, we sought to re-examine the effects of passive immunization in APPSWE/PS1dE9 Tg mice with targeted replacement of the murine Apoe gene for various human APOE alleles, which expression remains controlled by the native murine Apoe promoter [16, 17].”
BackgroundSelf-citationWeers, P. M. M., Narayanaswami, V., Choy, N., Luty, R., Hicks, L. D., Kay, C. M., & Ryan, R. O. (2002) · Biophysical Chemistry · doi:10.1016/s0301-4622(02)00300-9 · Cited by 33
Byrne, C. D. (1999) · Atherosclerosis · doi:10.1016/s0021-9150(99)00110-0 · Cited by 33
Mahmood, D. F. D., Abderrazak, A., Couchie, D., Lunov, O., Diderot, V., Syrovets, T., Slimane, M.-N., Gosselet, F., Simmet, T., Rouis, M., et al. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24319 · Cited by 34
Chapman, S., Sabo, T., Roses, A. D., & Michaelson, D. M. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00087-7 · Cited by 33
Li, Y., & Liu, L. (2014) · Lipids in Health and Disease · doi:10.1186/1476-511x-13-136 · Cited by 34
“ApoE2 knock-in mice were to easily develop hepertriglycerdemia and diet-induced obesity [53,54].”
BackgroundHuman apolipoprotein E isoforms differentially affect bone mass and turnover in vivo
Dieckmann, M., Beil, F. T., Mueller, B., Bartelt, A., Marshall, R. P., Koehne, T., Amling, M., Ruether, W., Cooper, J. A., Humphries, S. E., et al. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1757 · Cited by 34
“To reduce the complexity of the human situation and to circumvent the problems associated with the asymmetric allele frequency of the human APOE gene, we used a well-defined model system, developed previously by gene targeting, to replace the murine Apoe gene with the three respective human APOE alleles.((18,20,21))”
MethodApolipoprotein E is found in astrocytes but not in microglia in the normal mouse brain
Fujita, S. C., Sakuta, K., Tsuchiya, R., & Hamanaka, H. (1999) · Neuroscience Research · doi:10.1016/s0168-0102(99)00075-9 · Cited by 32
Jenner, A. M., Lim, W. L. F., Ng, M. P.-E., Wenk, M. R., Shui, G., Sharman, M. J., Gandy, S., & Martins, R. N. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.04.026 · Cited by 29
“These mice have been described previously (Piedrahita et al., 1992, Sullivan et al., 1997, Sullivan et al., 1998, Knouff et al., 1999).”
Luo, H., Faghankhani, M., Cao, Y., Uitto, J., & Li, Q. (2020) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.10.013 · Cited by 30
Yeiser, L. A., Villasana, L., & Raber, J. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.09.029 · Cited by 29
Pérez‐Díaz, S., Johnson, L. A., DeKroon, R. M., Moreno‐Navarrete, J. M., Álzate, Ó., Fernández‐Real, J. M., Maeda, N., & Arbonés-Mainar, J. M. (2014) · The FASEB Journal · doi:10.1096/fj.14-251165 · Cited by 30
“9), whose endogenous murine Apoe gene has been substituted by the human APOE*2 gene (10).”
BackgroundMethodSelf-citationIn silico analyses of deleterious missense SNPs of human apolipoprotein E3
Pires, Á. S., Porto, W. F., Franco, O. L., & de Alencar, S. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-01737-w · Cited by 29
“ApoE isoforms have been associated with several human disorders, such as Alzheimer’s disease 16, 17 , type III hyperlipoproteinemia 12, 18 , atherosclerosis 19 , telomere shortening 20 , impaired cognitive function 21 and infectious diseases 22, 23 .”
BackgroundInfluentialTailleux, A., Torpier, G., Mezdour, H., Fruchart, J., Staels, B., & Fiévet, C. (2003) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2003.08.001 · Cited by 28
Self-citationNuclear receptor mediated mechanisms of macrophage cholesterol metabolism
Nagy, Z. S., Czimmerer, Z., & Nagy, L. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.04.003 · Cited by 27
“Moreover, bexarotene, an anti-tumor agent that can activate RXR, was found to protect from atherosclerosis development in the human apo E2 knock-in mouse, a dyslipidemic model known to develop macrophage-laden lesions (Sullivan et al., 1998).”
Anticoagulant Effect of Dietary Fish Oil in Hyperlipidemia
Vanschoonbeek, K., Wouters, K., van der Meijden, P. E. J., van Gorp, P. J., Feijge, M. A. H., Herfs, M., Schurgers, L. J., Hofker, M. H., de Maat, M. P. M., & Heemskerk, J. W. M. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.156992 · Cited by 27
Influence of Western diet and APOE genotype on Alzheimer's disease risk
Sullivan, P. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104790 · Cited by 26
“There are no HFD studies in apoE2 TR mice likely due to the reduced interest in APOE2 and AD along with the fact that the apoE2 homozygous mice develop type III hypolipoproteinemia which complicates the interpretation of results [99].”
Self-citationKoutseff, A., Mittelhaeuser, C., Essabri, K., Auwerx, J. H., & Méziane, H. (2013) · Brain Research · doi:10.1016/j.brainres.2013.10.003 · Cited by 25
Baron, M., Leroyer, A. S., Majd, Z., Lalloyer, F., Vallez, E., Bantubungi, K., Chinetti, G., Delerive, P., Boulanger, C. M., Staels, B., et al. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.03.009 · Cited by 25
“The apoE2-KI mouse fed a Western diet is a model of early atherogenesis [32] in which atherosclerotic lesions are mainly composed of foam cells resembling fatty streaks in humans.”
MethodDeprince, A., Hennuyer, N., Kooijman, S., Pronk, A. C. M., Baugé, E., Liénard, V., Verrijken, A., Dirinck, E. L., Vonghia, L., Woitrain, E., et al. (2022) · Hepatology · doi:10.1002/hep.32631 · Cited by 24
“We next sought to challenge this system using the ApoE2- KI mouse, a model of combined hyperlipidemia, as a result of reduced affinity of ApoE2 for the LDLR.[34] Unlike in C57BL6/J mice, hepatic APOF overexpression in ApoE2- KI mice increased plasma ApoB levels (Figure S6A,B), indicating an increase in the number of c…”
Result(2004) · doi:10.1016/j.bbalip.2004.03.004 · Cited by 17
Self-citationNwabuisi‐Heath, E., LaDu, M. J., & Yu, C. (2012) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2012.04.003 · Cited by 26
Conway, V., Larouche, A., Alata, W., Vandal, M., Calon, F., & Plourde, M. (2014) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2014.09.007 · Cited by 26
Ribas, V., Palomer, X., Roglans, N., Rotllán, N., Fiévet, C., Tailleux, A., Julve, J., Escolá‐Gil, J. C., Blanco‐Vaca, F., & Escolá‐Gil, J. C. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.09.009 · Cited by 22
Protein Mediators of Sterol Transport Across Intestinal Brush Border Membrane
Brown, J. M., & Yu, L. (2010) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-90-481-8622-8_12 · Cited by 22
“…LXR activation reduces NPC1L1 mRNA levels by ~35% in the duodena of apolipoprotein (apo) E2-KI mice (lacking endogenous apoE but expressing human apoE2 (Sullivan et al., 1998) fed a Western diet (Duval et al., 2006), and ~50% in the small intestine of ABCB4 knockout mice (Kruit et al., 2005).”
BackgroundImpact of APOE genotype on prion-type propagation of tauopathy
Williams, T., Ruiz, A. J., Ruiz, A. M., Vo, Q., Tsering, W., Xu, G. M., McFarland, K. N., Giasson, B. I., Sullivan, P. M., Borchelt, D., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01359-y · Cited by 21
Self-citationApoE gene therapy to treat hyperlipidemia and atherosclerosis.
Harris, J., Evans, & Owen, J. S. (2006) · PubMed · Cited by 19
Dietary beta‐carotene and lutein metabolism is modulated by the APOE genotype
Huebbe, P., Lange, J., Lietz, G., & Rimbach, G. H. (2016) · BioFactors · doi:10.1002/biof.1284 · Cited by 21
Venzi, M., Tóth, M., Häggkvist, J., Bogstedt, A., Rachalski, A., Mattsson, A., Frumento, P., & Farde, L. (2017) · Journal of Alzheimer's Disease Reports · doi:10.3233/adr-170006 · Cited by 18
“Moreover, the fact that APOE2-TR mice display increased plasma cholesterol and lipid levels starting from an age of 2 months [25, 48], taken together with our data, suggests that the 2 allele may modulate peripheral energy metabolism before having an effect on cerebral metabolism.”
BackgroundGolden, L. R., Siano, D. S., Stephens, I. O., MacLean, S. M., Saito, K., Nolt, G. L., Funnell, J. L., Pallerla, A. V., Lee, S., Smith, C., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02094-y · Cited by 18
“E2-TR mice display a plasma lipid profile similar to the type III hyperlipoproteinemia found in ~5–10% of E2/E2 humans, particularly when challenged with a high-fat diet (HFD) 20 .”
APOE genotype and sex modulate Alzheimer’s disease pathology in aged EFAD transgenic mice
Balu, D., Valencia‐Olvera, A. C., Islam, Z., Mielczarek, C., Hansen, A. L., Ramos, T. M. P., York, J. M., LaDu, M. J., & Tai, L. M. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1279343 · Cited by 20
Huang, Z., Maeda, N., & Mazzone, T. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m017160 · Cited by 16
Self-citationStrattan, L. E., Britsch, D. R. S., Calulot, C. M., Maggard, R. S. J., Abner, E. L., Johnson, L. A., & Alilain, W. J. (2021) · eNeuro · doi:10.1523/eneuro.0464-20.2021 · Cited by 17
“March/April 2021, 8(2) ENEURO.0464-20.2021 eNeuro.org replacement mice) were backcrossed for at least 10 generations to the C57BL/6 background (Sullivan et al., 1997, 1998; Knouff et al., 1999).”
BackgroundInfluentialGenomic structure and genetic drift in C57BL/6 congenic metabolic mutant mice
Almodovar, A. J. O., Luther, R. J., Stonebrook, C. L., et al. (2013) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2013.06.019 · Cited by 16
Li, Q., Philip, V. M., Stearns, T. M., Bubier, J. A., King, B. L., Low, B. E., Wiles, M. V., Saeidian, A. H., Sundberg, B. A., Uitto, J., et al. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2019.04.023 · Cited by 15
Pig and Mouse Models of Hyperlipidemia and Atherosclerosis
Getz, G. S., & Reardon, C. A. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-1924-7_24 · Cited by 14
Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression and Metastasis
Adaku, N., Ostendorf, B. N., Mei, W., & Tavazoie, S. F. (2023) · Cancer Research · doi:10.1158/0008-5472.can-23-1252 · Cited by 15
Yao, X., Dai, C., Fredriksson, K., Lam, J. Y., Gao, M., Keeran, K. J., Nugent, G. Z., Qu, X., Yu, Z., Jeffries, N. O., et al. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00110.2011 · Cited by 14
The association between vascular function-related genes and age at natural menopause
van Disseldorp, J., Broekmans, F. J., Peeters, P. H. M., et al. (2008) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e31814cec52 · Cited by 15
“This mutation leads to type III hyperlipoproteinemia and its associated spontaneous atherosclerosis in 1% to 4% of homozygotes.(31,32)”
BackgroundWilliams, T., Bathe, T., Vo, Q., Sacilotto, P., McFarland, K. N., Ruiz, A. J., Hery, G. P., Sullivan, P. M., Borchelt, D., Prokop, S., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01581-2 · Cited by 16
“However, during aging, APOE2 homozygous mice, by themselves, show hyperlipoproteinemia and spontaneous atherosclerosis [14], consistent with phenome-wide association studies revealing harmful effects of APOE2 homozygosity on peripheral vascular homeostasis in humans [5].”
BackgroundSelf-citationPappolla, M. A., Refolo, L. M., Sambamurti, K., Zambón, D., & Duff, K. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240388 · Cited by 16
“One of the most frequently used mouse models to investigate the function of human ApoE in the central nervous system (CNS) is the human ApoE targeted replacement (TR) mice, developed in Nobuyo Maeda’s laboratory [47].”
Eck, M. V., Herijgers, N., van Dijk, K. W., Havekes, L. M., Hofker, M. H., Groot, P. H. E., & van Berkel, T. J. C. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.1.119 · Cited by 14
Papaioannou, I., Simons, J. P., & Owen, J. S. (2012) · Cardiology Research and Practice · doi:10.1155/2012/148796 · Cited by 15
Chouinard‐Watkins, R., Pinçon, A., Coulombe, J.-D., Spencer, R., Massenavette, L., & Plourde, M. (2016) · Journal of Nutrition · doi:10.3945/jn.116.230052 · Cited by 13
Apolipoprotein E Isoform-specific changes related to stress and trauma exposure
Torres, E. R. S., Luo, J., Boehnlein, J. K., Towns, D., Kinzie, J. D., DeBarber, A. E., & Raber, J. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01848-7 · Cited by 15
Lee, J. H., Jun, H., Jia, Y., Kim, W., Choi, S., & Lee, S. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf202910u · Cited by 13
Loss of apolipoprotein E exacerbates the neonatal lethality of the Smith-Lemli-Opitz syndrome mouse
Solcà, C., Pandit, B., Yu, H., Tint, G. S., & Patel, S. B. (2007) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2006.11.009 · Cited by 12
Hinsdale, M. E., Sullivan, P. M., Mezdour, H., & Maeda, N. (2002) · Journal of Lipid Research · doi:10.1194/jlr.m200103-jlr200 · Cited by 12
“inant apoB containing lipoprotein accumulating in the Apoe2/2 mice contains apoB-48 (5).”
BackgroundMethodSelf-citationAAV1-LPLS447X gene therapy reduces hypertriglyceridemia in apoE2 knock in mice
Rip, J., van Dijk, K. W., Sierts, J. A., Kastelein, J. J. P., Twisk, J., & Kuivenhoven, J. A. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2006.08.008 · Cited by 11
Lloyd, G. M., Long, B., Quintin, S., Sorrentino, Z. A., Gorion, K.-M. M., Bell, B. M., Carrillo, D., Sullivan, P., Borchelt, D., & Giasson, B. I. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01623-9 · Cited by 11
“APOE targeted replacement mice with either the homozygous APOE ε3 or APOE ε4 humanized alleles [23, 46, 47] were obtained from Dr.”
MethodSelf-citationM1-Activated Macrophages Migration, A Marker of Aortic Atheroma Progression
Bessaad, A., Sigovan, M., Alsaid, H., Souza, G. D., Provost, N., Majd, Z., Ménager, C., Honnorat, J., Lagarde, F., Nighoghossian, N., et al. (2010) · Investigative Radiology · doi:10.1097/rli.0b013e3181d78030 · Cited by 11
“Under a standard diet, these mice develop atheroma, characterized by the almost exclusive presence of macrophages.(16) A total of 19 one-year-old female ApoE2 ki mice (Genfit, Lille, France) and 5 wild type C57BL/6J, all on chow diet, (Charles River, l’Arbresles, France) were imaged.”
BackgroundDose- and ApoE Isoform-Dependent Cognitive Injury after Cranial56Fe Irradiation in Female Mice
Villasana, L., Dayger, C. A., & Raber, J. (2013) · Radiation Research · doi:10.1667/rr3210.1 · Cited by 11
“Human apoE targeted replacement (TR) mice, generated as described (12, 13), were provided for breeding by Dr.”
BackgroundVillasana, L., Pfankuch, T., & Raber, J. (2010) · Radiation and Environmental Biophysics · doi:10.1007/s00411-010-0290-4 · Cited by 11
“…human data, we previously reported that in human apoE targeted replacement mice expressing human apoE under the control of the mouse apoE promoter (Sullivan et al. 1997, 1998; Knouff et al. 1999) 2-month-old female apoE3 and apoE4 mice irradiated with 137Cs show hippocampusdependent cognitive…”
BackgroundMethodEzra, Y., Oron, L., Moskovich, L., Roses, A. D., Beni, S. M., Shohami, E., & Michaelson, D. M. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00436-6 · Cited by 11
Sanganahalli, B. G., Mihailovic, J. M., Vekaria, H. J., Coman, D., Yackzan, A. T., Flemister, A., Aware, C. B., Wenger, K., Hubbard, W. B., Sullivan, P. G., et al. (2024) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x241261942 · Cited by 12
“23 The healthy young E4FAD mice were fed with rapamycin before they started to develop A b and cognitive impairments.”
Self-citationHolden, S. J., Kundu, P., Torres, E. R. S., Sudhakar, R., Krenik, D., Grygoryev, D., Turker, M. S., & Raber, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.767558 · Cited by 10
Gerritsen, G., van der Hoogt, C. C., Schaap, F. G., Voshol, P. J., Kypreos, K. E., Maeda, N., Groen, A. K., Havekes, L. M., Rensen, P. C. N., & van Dijk, K. W. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800009-jlr200 · Cited by 11
Self-citationDiaz, J. R., Martá-Ariza, M., Khodadadi‐Jamayran, A., Heguy, A., Tsirigos, A., Pankiewicz, J. E., Sullivan, P. M., & Sadowski, M. J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.845291 · Cited by 11
Self-citationBadea, A., Li, D., Niculescu, A. R., Anderson, R. J., Stout, J. A., Williams, C. L., Colton, C. A., Maeda, N., & Dunson, D. B. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.848654 · Cited by 9
Self-citationGarcia‐Caraballo, S., Comhair, T. M., Dejong, C. H. C., Lamers, W. H., & Köhler, E. S. (2014) · British Journal Of Nutrition · doi:10.1017/s0007114514001986 · Cited by 9
“The high concentrations of plasma (V)LDL in APOE2ki mice arise as a result of the lower clearance of these lipoproteins and their lipid load((16)).”
BackgroundInfluentialNanoparticles for Diagnosis and/or Treatment of Alzheimer's Disease
Antimisiaris, S. G., Mourtas, S., Markoutsa, E., Σκούρας, Α., & Παπαδιά, Κ. (2014) · Advanced Healthcare Materials · doi:10.1002/9781118774205.ch4 · Cited by 11
Features of Lipid Metabolism in Humanized ApoE Knockin Rat Models
Wu, Y., Johnson, G., Zhao, F., Wu, Y., Zhao, G., Brown, A. J., You, S., Zou, M., & Song, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158262 · Cited by 10
“The ApoE expression level in the plasma and livers of hApoE2 mice was higher [19,20,38,43], while we only observed a higher expression of ApoE in the livers of the hApoE2 rats.”
BackgroundBoutros, S. W., Zimmerman, B., Nagy, S. C., Unni, V. K., & Raber, J. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-01966-8 · Cited by 9
Grenon, M. B., Papavergi, M.-T., Bathini, P., Sadowski, M. J., & Lemere, C. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115754 · Cited by 7
“…comparing the patient risk for vascular adverse events in anti-A β immunotherapy, we selected an AD transgenic mouse model (APPswe/PS1dE9 [44–47]) in which murine APOE has been replaced by human APOE4 or human APOE3 , and its expression remains controlled by the native murine APOE promoter [48,49].”
MethodApolipoprotein E loss of function: Influence on murine brain markers of physiology and pathology
Buchanan, H. M., Hull, C. E., Barraza, M. C., Delibegović, M., & Platt, B. (2022) · Aging Brain · doi:10.1016/j.nbas.2022.100055 · Cited by 7
“This has benefited from the generation of ApoE transgenic models such as the targeted replacement mice, in which the endogenous ApoE gene has been replaced by a human isoform [28,63,62].”
BackgroundMouse models as tools for dissecting disorders of lipoprotein metabolism
Marschang, P., & Herz, J. (2003) · Seminars in Cell and Developmental Biology · doi:10.1016/s1084-9521(02)00169-6 · Cited by 7
“[35] Sullivan PM, Mezdour H, Quarfordt SH, Maeda N.”
Background[Experimental models of cardiovascular disease].
Hernández, A. G., Ramírez-Tortosa, M. C., García, M. C. A., & García, M. D. M. (2007) · PubMed · Cited by 7
Editorial: Exploring Lipid-related Treatment Options for the Treatment of NASH
Rizzo, M., Montalto, G., & Vinciguerra, M. (2014) · Current Vascular Pharmacology · doi:10.2174/157016111205140926155515 · Cited by 6
“Apo E2 has a decreased affinity for the LDL receptor, leading to a lipoprotein profile resembling human type III hyperlipoproteinaemia [34].”
BackgroundMouse Models in Cardiology Research
Madamanchi, A. (2020) · McGill Journal of Medicine · doi:10.26443/mjm.v8i1.516 · Cited by 5
Chaklai, A., Rhea, E. M., O’Niel, A., Babin, A., Weaver, R. R., Pemberton, S., Banks, W. A., & Raber, J. (2024) · Scientific Reports · doi:10.1038/s41598-024-62053-8 · Cited by 5
“Male and female human apoE targeted replacement (TR) mice, models originally generated by Dr. Patrick Sullivan 66–68 were used in this study.”
MethodDurumutla, H. B., Haller, A. M., Noble, G., Prabakaran, A. D., McFarland, K., Latimer, H., Rajput, A., Akinborewa, O., Namjou‐Khales, B., Hui, D. Y., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci190180 · Cited by 7
“The hAPOE * 2/ * 2 mice are well-established transgenic mice known for their susceptibility to atherosclerosis while maintaining cholesterol distribution across all 3 major lipoprotein compartments (47, 48), unlike other atherogenic backgrounds like ApoE-KO.”
Moon, H. S., Mahzarnia, A., Stout, J. A., Anderson, R. J., Strain, M., Tremblay, J. T., Han, Z. Y., Niculescu, A., MacFarlane, A., King, J., et al. (2023) · Brain Structure and Function · doi:10.1007/s00429-023-02731-x · Cited by 4
“…poses a specific challenge, in that mice with the APOE2 allele exhibit a higher incidence of hyperlipoproteinemia compared to humans (Patrick M. Sullivan et al. 1998a, b), and there is a lack of consensus regarding their performance in learning and memory tests (Badea et al. 2022; Watson et…”
Jo, D. H., Lee, J. H., Jun, H., Kim, J. H., Wen, Q., Hoang, M. H., Yu, Y., Kim, J. H., Kim, J. H., & Lee, S. (2015) · Genetics and Molecular Research · doi:10.4238/2015.march.13.14 · Cited by 5
“ApoE2 mice did not express mouse apoE, but instead expressed human apoE2 (Sullivan et al., 1998).”
BackgroundVillasana, L., Akinyeke, T. O., Weber, S. J., & Raber, J. (2017) · Oncotarget · doi:10.18632/oncotarget.20603 · Cited by 5
“Patrick Sullivan [42, 43] and bred in our colony, were used for the present study.”
MethodMalek, G., Mace, B. E., Saloupis, P., Schmechel, D. E., Rickman, D. W., Sullivan, P. M., & Rickman, C. B. (2007) · Springer eBooks · doi:10.1007/0-387-32442-9_17 · Cited by 5
“On the other hand, 5- 10% of APOE2 humans will develop Type III hyperlipoproteinemia, whereas 100% of APOE2 TR mice on a high fat diet develop Type III hyperlipoproteinemia ( Sullivan et al., 1998 ).”
BackgroundSelf-citationHuman ApoE2 Endows Stronger Contractility in Rat Cardiomyocytes Enhancing Heart Function
Wu, Y., Zhao, F., Sure, V. N. L. R., Ibrahim, A. D., Yu, C., Carr, S. M., & Song, P. (2023) · Cells · doi:10.3390/cells12030347 · Cited by 5
Animal Models of Exercise and Cardiometabolic Disease
Dong, G., RYAN, T. E., & Esser, K. A. (2025) · Circulation Research · doi:10.1161/circresaha.124.325704 · Cited by 4
Cho, J., Alexander, K. L., Ferrell, J. L., Johnson, L. A., Estus, S., & D’Orazio, S. E. F. (2023) · Infection and Immunity · doi:10.1128/iai.00251-23 · Cited by 3
O’Niel, A., Pederson, A., Saltontall, E., Nguyen, K., Pantoja, M., Chaudhari, M., Sandholm, P., Yoon, E., Harrison, H. F., Boutros, S. W., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1473366 · Cited by 3
Vogel, H. G., & Vogel, W. H. (1997) · Springer eBooks · doi:10.1007/978-3-662-03333-3_12 · Cited by 3
Cardiovascular DiseaseMouse Models of Atherosclerosis
MAEDA, N., CGIVENS, R., & LReddick, R. (2007) · Elsevier eBooks · doi:10.1016/b978-012369454-6/50070-4 · Cited by 3
Self-citationVogel, H. G. (2007) · Springer eBooks · doi:10.1007/978-3-540-70995-4_14 · Cited by 3
Lee, S. M., Kim, J. W., Jeong, Y.-H., Kim, S. E., Kim, Y. J., Moon, S. J., Lee, J., Kim, K. J., Kim, M., & Kang, M. (2014) · Asian-Australasian Journal of Animal Sciences · doi:10.5713/ajas.2014.14222 · Cited by 2
“In previous studies, knock-in mice that targeted replacement of the mouse apolipoprtein E gene with the human apolipoprotein E (human APOE) allele were produced, and the human APOE gene was expressed under the natural regulation of this protein by the gene regulatory sequence of the mouse APOE gene (Sullivan et al., 1…”
MethodFagla, B. M., York, J. M., Christensen, A., Rosa, C. D., Balu, D., Pike, C. J., Tai, L. M., & Buhimschi, I. A. (2024) · Scientific Reports · doi:10.1038/s41598-024-66489-w · Cited by 2
Experimental Models of Oxidative Stress Related to Cardiovascular Diseases and Diabetes
Mesa, M. D., Aguilera, C. M., & Gil, Á. (2011) · Humana Press eBooks · doi:10.1007/978-1-60761-956-7_2 · Cited by 2
“These individuals have lower VLDL clearance, and thus develop atherosclerosis in spite of a normal diet [ 41 ].”
BackgroundLu, H., Zhang, J., Chen, Y. E., & Garcia-Barrio, M. T. (2021) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-021-07175-1 · Cited by 2
Differential Antiatherogenic Effects of PPARα Versus PPARγ Agonists
Camejo, G. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000181034.54148.8d · Cited by 2
Metadata
- Authors
- Sullivan, P. M., Mezdour, H., Quarfordt, S. H., & Maeda, N.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Duke University (US)
- ORCID
- Sullivan, P M
- Venue
- Journal of Clinical Investigation
- Published
- 1998-07-01
- Volume
- 102
- Issue
- 1
- Pages
- 130-135
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC509074
- OpenAlex
- W2009182898
- Semantic Scholar
- 5c70c14be49e1fca602aaf2a63c7aa5e2341ef41
- Cited by
- 264
- References
- 33
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 10 · 2023: 19 · 2022: 15 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 9 · 2014: 16 · 2013: 11 · 2012: 14
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 42630)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- type III hyperlipoproteinemia, apolipoprotein E isoforms, spontaneous atherosclerosis, xanthoma, VLDL clearance, serum cholesterol, plasma triglycerides, atherogenic diet
- MeSH terms
- Animals, Apolipoproteins E, Arteriosclerosis, Cholesterol, Clofibrate, Dietary Fats, Female, Humans, Hyperlipoproteinemia Type III, Lipoproteins, VLDL, Male, Triglycerides, Gene Targeting, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
