A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal-fetal lipid transport in mice.

A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal-fetal lipid transport in mice.
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DOI:
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发表时间:
1996-02
影响因子:
6.5
通讯作者:
Robert V Farese;S. Cases;S. Ruland;H. Kayden;J. Wong;S. Young;R. Hamilton
Robert V Farese;S. Cases;S. Ruland;H. Kayden;J. Wong;S. Young;R. Hamilton
中科院分区:
生物学2区
文献类型:
--
作者:
Robert V Farese;S. Cases;S. Ruland;H. Kayden;J. Wong;S. Young;R. Hamilton

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载脂蛋白(apo)B是肠道和肝脏合成及分泌富含甘油三酯的脂蛋白所必需的主要结构成分,在哺乳动物的卵黄囊脏层内胚层中高度表达,尽管其在该组织中的功能至今尚不清楚。小鼠apoB基因的破坏会导致胚胎致死(约9.5 - 10.5天)。在此我们证明,apoB在卵黄囊脏层内胚层细胞的胚胎发育早期正常表达,且这种表达与含apoB的脂蛋白的合成及分泌有关。脏层内胚层中缺乏apoB导致细胞内脂滴积聚,分泌途径中缺乏脂蛋白,以及apoB - / - 胚胎组织中胆固醇和α - 生育酚浓度降低。apoB + / - 胚胎的脏层内胚层表现出中间表型。我们的结果表明,apoB在通过卵黄囊介导的含apoB脂蛋白的合成及分泌将脂质营养物质运输到发育中的小鼠胚胎方面起着至关重要的作用。
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.