A genetic model for absent chylomicron formation: mice producing apolipoprotein B in the liver, but not in the intestine.
A genetic model for absent chylomicron formation: mice producing apolipoprotein B in the liver, but not in the intestine.
复制标题
乳糜微粒形成缺失的遗传模型：小鼠在肝脏中产生载脂蛋白 B，但在肠道中不产生。
DOI：
10.1172/jci118365
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
FareseJr,RV
中科院分区：
文献类型：
--
作者：
Young,SG;Cham,CM;Pitas,RE;Burri,BJ;Connolly,A;Flynn,L;Pappu,AS;Wong,JS;Hamilton,RL;FareseJr,RV
肠道乳糜微粒的形成对于膳食脂肪和脂溶性维生素（例如，视黄醇、α-生育酚）。载脂蛋白B在肠道乳糜微粒和肝脏VLDL的形成中起着重要的结构作用。我们已经培育出转基因小鼠，它们在肝脏中表达载脂蛋白B，但在肠道中不表达。电镜观察，这些小鼠的肠上皮细胞缺乏新生的乳糜微粒的内质网和高尔基体。由于这些小鼠不能形成乳糜微粒，肠绒毛肠细胞大量充满脂肪，这些脂肪包含在胞质脂滴中。这些小鼠正常吸收D-木糖，但实际上没有吸收视黄醇棕榈酸酯或胆固醇。血浆中的α-生育酚水平极低。值得注意的是，肠道中乳糜微粒合成的缺乏似乎对肝脏产生的含载脂蛋白B的脂蛋白的血浆水平没有显著影响。缺乏肠道apo B表达的小鼠代表了脂肪和脂溶性维生素吸收缺陷的第一个遗传模型，并为研究营养和脂蛋白代谢提供了有用的动物模型。
The formation of chylomicrons by the intestine is important for the absorption of dietary fats and fat-soluble vitamins (e.g., retinol, alpha-tocopherol). Apo B plays an essential structural role in the formation of chylomicrons in the intestine as well as the VLDL in the liver. We have developed genetically modified mice that express apo B in the liver but not in the intestine. By electron microscopy, the enterocytes of these mice lacked nascent chylomicrons in the endoplasmic reticulum and Golgi apparatus. Because these mice could not form chylomicrons, the intestinal villus enterocytes were massively engorged with fat, which was contained in cytosolic lipid droplets. These mice absorbed D-xylose normally, but there was virtually no absorption of retinol palmitate or cholesterol. The levels of alpha-tocopherol in the plasma were extremely low. Of note, the absence of chylomicron synthesis in the intestine did not appear to have a significant effect on the plasma levels of the apo B-containing lipoproteins produced by the liver. The mice lacking intestinal apo B expression represent the first genetic model of defective absorption of fats and fat-soluble vitamins and provide a useful animal model for studying nutrition and lipoprotein metabolism.Images