Farese R V, Cases S, Ruland S L, Kayden H J, Wong J S, Young S G, Hamilton R L
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141-9100, USA.
J Lipid Res. 1996 Feb;37(2):347-60.
Apolipoprotein (apo) B, the principal structural component necessary for the synthesis and secretion of triglyceride-rich lipoproteins by the intestine and liver, is highly expressed in the yolk sac visceral endoderm of mammals, although its function in this tissue has been hitherto unclear. Disruption of the apoB gene in mice results in embryonic lethality (approximately 9.5 - 10.5 d). Here we demonstrate that apoB is normally expressed at early time points in embryonic development in yolk sac visceral endodermal cells, and that this expression is associated with the synthesis and secretion of apoB-containing lipoproteins. The lack of apoB in the visceral endoderm resulted in an accumulation of intracellular lipid droplets, an absence of lipoproteins from the secretory pathway, and reduced concentrations of cholesterol and alpha-tocopherol in tissues of apoB-/- embryos. Visceral endoderm of apoB+/- embryos exhibited an intermediate phenotype. Our results suggest that apoB plays an essential role in the transport of lipid nutrients to the developing mouse embryo via the yolk sac-mediated synthesis and secretion of apoB-containing lipoproteins.
载脂蛋白(apo)B是肠道和肝脏合成及分泌富含甘油三酯脂蛋白所必需的主要结构成分,在哺乳动物的卵黄囊脏内胚层中高度表达,尽管其在该组织中的功能迄今尚不清楚。小鼠载脂蛋白B基因的破坏会导致胚胎致死(约9.5 - 10.5天)。在此我们证明,载脂蛋白B在胚胎发育早期卵黄囊脏内胚层细胞中正常表达,且这种表达与含载脂蛋白B的脂蛋白的合成及分泌相关。脏内胚层中载脂蛋白B的缺失导致细胞内脂质小滴积聚、分泌途径中缺乏脂蛋白,以及载脂蛋白B基因敲除胚胎组织中胆固醇和α-生育酚浓度降低。载脂蛋白B基因杂合子胚胎的脏内胚层表现出中间表型。我们的结果表明,载脂蛋白B通过卵黄囊介导含载脂蛋白B的脂蛋白的合成及分泌,在向发育中的小鼠胚胎转运脂质营养物质方面发挥着重要作用。