Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1-/- mice
Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1-/- mice
复制标题
DOI：
10.1194/jlr.m030494
复制
发表时间：
2012-12-01
影响因子：
6.5
通讯作者：
Davidson, Nicholas O.
中科院分区：
文献类型：
--
作者：
Blanc, Valerie;Xie, Yan;Davidson, Nicholas O.
肠载脂蛋白B（apoB）mRNA在催化脱氨酶apobec-1的介导下进行C至U编辑，导致apoB 48的翻译。Apobec 1（-/-）小鼠仅产生apoB 100，并分泌比野生型（WT）小鼠中观察到的更大的乳糜微粒。在这里，我们表明，肠apobec-1表达的转基因救援（Apobec 1（Int/O））恢复了体内apoB mRNA的C到U RNA编辑，包括位置6666处的典型位点，以及WT小鼠中存在的大约20个其他新鉴定的下游位点。Apobec 1（Int/O）小鼠的小肠仅产生apoB 48，肝脏仅产生apoB 100。与Apobec 1（-/-）小鼠相比，Apobec 1（Int/O）小鼠的血清乳糜微粒更小，Apobec 1（Int/O）小鼠血清apoB 48的主要部分在小于乳糜微粒的脂蛋白中迁移，即使这些小鼠被喂食高脂饮食。由于Apobec 1（Int/O）小鼠的apoB 48仅来源于肠道，且肠道apoB 48的合成和分泌速率与WT小鼠相当，因此我们能够推断WT小鼠血清apoB 48的主要来源部位。我们的研究结果表明，WT小鼠中不到25%的血清apoB 48来自肠道，大部分来自肝脏。Blanc，V.，Y. Xie，J. Luo，S. Kennedy和N. O.戴维森. Apobec-1的肠道特异性表达挽救了Apobec 1（-/-）小鼠中载脂蛋白B RNA编辑并改变了乳糜微粒的产生《脂类研究杂志》，2012年。53：2643-2655。
Intestinal apolipoprotein B (apoB) mRNA undergoes C-to-U editing, mediated by the catalytic deaminase apobec-1, which results in translation of apoB48. Apobec1(-/-) mice produce only apoB100 and secrete larger chylomicron particles than those observed in wild-type (WT) mice. Here we show that transgenic rescue of intestinal apobec-1 expression (Apobec1(Int/O)) restores C-to-U RNA editing of apoB mRNA in vivo, including the canonical site at position 6666 and also at approximately 20 other newly identified downstream sites present in WT mice. The small intestine of Apobec1(Int/O) mice produces only apoB48, and the liver produces only apoB100. Serum chylomicron particles were smaller in Apobec1(Int/O) mice compared with those from Apobec1(-/-) mice, and the predominant fraction of serum apoB48 in Apobec1(Int/O) mice migrated in lipoproteins smaller than chylomicrons, even when these mice were fed a high-fat diet. Because apoB48 arises exclusively from the intestine in Apobec1(Int/O) mice and intestinal apoB48 synthesis and secretion rates were comparable to WT mice, we were able to infer the major sites of origin of serum apoB48 in WT mice. Our findings imply that less than 25% of serum apoB48 in WT mice arises from the intestine, with the majority originating from the liver.-Blanc, V., Y. Xie, J. Luo, S. Kennedy, and N. O. Davidson. Intestine-specific expression of Apobec-1 rescues apolipoprotein B RNA editing and alters chylomicron production in Apobec1(-/-) mice. J. Lipid Res. 2012. 53: 2643-2655.