A young type III hyperlipoproteinemic patient associated with apolipoprotein E deficiency

Mabuchi, Hiroshi; Itoh, Hideaki; Takeda, Masayoshi; Kajinami, Kouji; Wakasugi, Takanobu; Koizumi, Junji; Takeda, Ryoyu; Asagami, Chidori

doi:10.1016/0026-0495(89)90249-7

Cited by 65 publications

(39 citation statements)

References 26 publications

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“…To investigate whether these mice could also develop grossly visible xanthomas, a group of 30 homozy gous mutant mice and 30 wild-type littermates were fed the HFC diet for a prolonged time. About one third of the apo E-deficient mice had indeed xanthomas 5 months treatment abnormalities 4. Discussion This paper demonstrates that apo E-deficient mice fed a hypercholesterolemic diet for 14 weeks develop severe xanthomatosis.…”

Section: Resultsmentioning

confidence: 60%

Atypical xanthomatosis in apolipoprotein E-deficient mice after cholesterol feeding

Ree

Gijbels²,

Broek

et al. 1995

Atherosclerosis

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Apolipoprotein (apo) E-deficient mice were fed a hypercholesterolemic diet for 14 weeks. Mean serum cholesterol levels rose to 37.5 mM. Upon complete necroscopy, massive xanthomatous lesions were noticed in various tissues, with a predilection for subcutaneous and peritendinous tissues, while control animals on the same diet (3.4 mM serum cho lesterol) and apo E-deficient mice on a regular chow diet (20 mM serum cholesterol) did not show such lesions. Also, apo E3-Leiden transgenic mice fed a high fat diet, with 60 mM of serum cholesterol, did not exhibit any xanthomatosis. The xanthomatous lesions found in the Apoe knock-out mouse clearly differed in location from xanthomas previously found in low density lipoprotein receptor-deficient mice. We conclude that the lack of apo E results in atypical dis seminated xanthomatosis, suggesting that apo E has an important role in determining the tissue distribution of choles terol deposition.

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Section: Resultsmentioning

confidence: 60%

Atypical xanthomatosis in apolipoprotein E-deficient mice after cholesterol feeding

Ree

Gijbels²,

Broek

et al. 1995

Atherosclerosis

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“…1993). Apo E is also at the center of interest, because patients with apo E deficiency have a lipoprotein pattern resembling that seen in type III hyperlipoproteinemia and also develop atherosclerosis and xanthomas (Ghiselli et al 1981, Schaeffer et al 1986, Mabuchi et al 1989, Mahley & Rall 1989. Moreover, a common genetic variation of apo E in human populations is also known (Zannis et al 1982).…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E-deficient mice created by systemic administration of antisense oligodeoxynucleotides: a new model for lipoprotein metabolism studies

Morishita

Gibbons²,

Kaneda³

et al. 2002

Journal of Endocrinology

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Atherosclerotic cardiovascular disease results from complex interactions among multiple genetic and environmental factors. Thus, it is important to elucidate the influence of each factor on cholesterol metabolism. For this purpose, transgenic/gene-targeting technology is a powerful tool for studying gene functions. However, this technology has several disadvantages such as being time consuming and expensive. Accordingly, we established new animal models using in vivo gene transfer technology. In this study, we examined the feasibility of the creation of a new animal model for the study of atherosclerosis. We hypothesized that apolipoprotein (apo) E-deficient mice can be created by systemic administration of antisense apo E oligodeoxynucleotides (ODN) coupled to the HVJliposome complex. Initially, we examined the localization and cellular fate of FITC-labeled antisense ODN administered intravenously. FITC-labeled ODN transfection by the HVJ-liposome method resulted in fluorescence in the liver, spleen and kidney, but not in other organs such as brain. Moreover, fluorescence with the HVJ-liposome method was sustained for up to 2 weeks after transfection, which resulted in a striking difference from transfection of ODN alone or ODN in liposomes without HVJ, which showed rapid disappearance of fluorescence (within 1 day). Given these unique characteristics of the HVJ-liposome method, we next examined transfection of antisense apo E ODN by intravenous administration. Transfection of antisense apo E ODN resulted in a marked reduction of apo E mRNA levels in the liver, but no change in apo B and -actin mRNA levels. In mice fed a normal diet, a transient increase in cholesterol and triglyceride levels was observed in the antisense apo E-treated group, but they returned to normal levels by 6 days after transfection. Similar findings were also found in mice fed a high cholesterol diet. Neither scrambled nor mismatched ODN resulted in any increase in cholesterol. To make chronic hypercholesterolemic mice, we therefore performed repeated injections of apo E antisense ODN. Whenever antisense apo E ODN were injected, mice showed a transient increase in cholesterol and triglyceride. Cumulative administration of antisense apo E ODN resulted in a sustained increase in cholesterol for up to 3 weeks after the last transfection. Finally, mice treated with repeated injections of antisense apo E every week developed sustained hypercholesterolemia and hypertriglyceridemia until withdrawal of injections. Apolipoprotein-deficient mice created by intravenous administration of antisense ODN are a promising new animal model to help understand the role of apolipoprotein in vivo and develop a new drug therapy targeting apolipoprotein.

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“…non-detectable apo-E. 13,14 Other cases of apo-E de¢-ciency have been reported by Mabuchi et al 15 and by Kurosaka et al, 16 the latter due to depressed mRNA of normal size. All of the described mutations lead in their homozygous forms to apo-E de¢ciency, 9--11,14--16 elevated serum lipid indices 9--11,14--16 and abnormally high VLDL-cholesterol/serum triglyceride ratios, 9--11,14,15 the latter being indicative for FD.…”

Section: Biochemical Consequencesmentioning

confidence: 92%

Discovery and consequences of apolipoprotein-ε_3Groningen: a G-insertion in codon 95/96 that is predicted to cause a premature stop codon

Dijck-Brouwer¹,

Doormaal²,

Kema³

et al. 2005

Ann Clin Biochem

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Discovery and consequences of apolipoprotein-e 3Groningen : a G-insertion in codon 95/96 that is predicted to cause a premature stop codon Background We found an unexplained, persistent discrepancy between the outcomes of two apolipoprotein-E (apo-E) genotyping methods for a patient with features of familial dysbetalipoproteinaemia (FD). Polymerase chain reactionrestriction fragment length polymorphism resulted in the apo-e 2 /e 2 genotype, whereas minisequencing indicated apo-e 2 /e 3 . The discrepancy was predicted to derive from a novel mutation.

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A young type III hyperlipoproteinemic patient associated with apolipoprotein E deficiency

Cited by 65 publications

References 26 publications

Atypical xanthomatosis in apolipoprotein E-deficient mice after cholesterol feeding

Atypical xanthomatosis in apolipoprotein E-deficient mice after cholesterol feeding

Apolipoprotein E-deficient mice created by systemic administration of antisense oligodeoxynucleotides: a new model for lipoprotein metabolism studies

Discovery and consequences of apolipoprotein-ε_3Groningen: a G-insertion in codon 95/96 that is predicted to cause a premature stop codon

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A young type III hyperlipoproteinemic patient associated with apolipoprotein E deficiency

Cited by 65 publications

References 26 publications

Atypical xanthomatosis in apolipoprotein E-deficient mice after cholesterol feeding

Atypical xanthomatosis in apolipoprotein E-deficient mice after cholesterol feeding

Apolipoprotein E-deficient mice created by systemic administration of antisense oligodeoxynucleotides: a new model for lipoprotein metabolism studies

Discovery and consequences of apolipoprotein-ε3Groningen: a G-insertion in codon 95/96 that is predicted to cause a premature stop codon

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Discovery and consequences of apolipoprotein-ε_3Groningen: a G-insertion in codon 95/96 that is predicted to cause a premature stop codon