文章基本信息

标题：Hyperlipidemia in APOE2 transgenic mice is ameliorated by a truncated apoE variant lacking the C-terminal domain
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作者：Gery Gerritsen ; Kyriakos E. Kypreos ; André van der Zee 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2003
卷号：44
期号：2
页码：408-414
DOI：10.1194/jlr.M200313-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Familial dysbetalipoproteinemia associated with the apolipoprotein E2 (APOE2) genotype is a recessive disorder with low penetrance. We have investigated whether additional expression of full-length APOE3, APOE4, or a truncated variant of APOE4 (APOE4-202) can reduce APOE2- associated hyperlipidemia. This was achieved using adenovirus-mediated gene transfer to mice transgenic for human APOE2 and deficient for endogenous Apoe (APOE2. Apoe ⁻ ^/ ⁻ mice). The hyperlipidemia of APOE2. Apoe ⁻ ^/ ⁻ mice was readily aggravated by APOE3 and APOE4 overexpression. Only a very low dose of APOE4 adenovirus was capable of reducing the serum cholesterol and triglyceride (TG) levels. Expression of higher doses of APOE4 was associated with an increased VLDL-TG production rate and the accumulation of TG-rich VLDL in the circulation. In contrast, a high dose of adenovirus carrying APOE4-202 reduced both the cholesterol and TG levels in APOE2. Apoe ⁻ ^/ ⁻ mice. Despite the absence of the C-terminal lipid-binding domain, APOE4-202 is apparently capable of binding to lipoproteins and mediating hepatic uptake. Moreover, overexpression of APOE4-202 in APOE2. Apoe ⁻ ^/ ⁻ mice does not aggravate their hypertriglyceridemia. These results extend our previous analyses of APOE4-202 expression in Apoe ⁻ ^/ ⁻ mice and demonstrate that apoE4-202 functions even in the presence of clearance-defective apoE2. Thus, apoE4-202 is a safe and efficient candidate for future therapeutic applications.