HOMOZYGOUS DISRUPTION OF THE MURINE MDR2 P-GLYCOPROTEIN GENE LEADS TO A COMPLETE ABSENCE OF PHOSPHOLIPID FROM BILE AND TO LIVER-DISEASE
HOMOZYGOUS DISRUPTION OF THE MURINE MDR2 P-GLYCOPROTEIN GENE LEADS TO A COMPLETE ABSENCE OF PHOSPHOLIPID FROM BILE AND TO LIVER-DISEASE
复制标题
DOI：
10.1016/0092-8674(93)90380-9
复制
发表时间：
1993-11-05
期刊：
影响因子：
64.5
通讯作者：
BORST, P
中科院分区：
文献类型：
--
作者：
SMIT, JJM;SCHINKEL, AH;BORST, P
在哺乳动物中发现了两种类型的 P-糖蛋白：转运药物的 P-糖蛋白和无法转运疏水性抗癌药物的第二种类型。后者由人类 MDR3（也称为 MDR2）和小鼠 mdr2 基因编码，其组织分布（肝细胞的胆小管膜、B 细胞、心脏和肌肉）表明其具有特殊的代谢功能。我们已经培育出了 mdr2 基因破坏的纯合子小鼠。这些小鼠患上肝脏疾病，这似乎是由于肝脏完全无法将磷脂分泌到胆汁中引起的。等位基因被破坏的杂合小鼠没有可检测到的肝脏病理学，但胆汁中磷脂的水平只有一半。我们得出结论，mdr2 P-糖蛋白在磷脂酰胆碱分泌到胆汁中具有重要作用，并假设它可能是磷脂转运蛋白或磷脂翻转酶。
Two types of P-glycoprotein have been found in mammals: the drug-transporting P-glycoproteins and a second type, unable to transport hydrophobic anticancer drugs. The latter is encoded by the human MDR3 (also called MDR2) and the mouse mdr2 genes, and its tissue distribution (bile canalicular membrane of hepatocytes, B cells, heart, and muscle) suggests a specialized metabolic function. We have generated mice homozygous for a disruption of the mdr2 gene. These mice develop a liver disease that appears to be caused by the complete inability of the liver to secrete phospholipid into the bile. Mice heterozygous for the disrupted allele had no detectable liver pathology, but half the level of phospholipid in bile. We conclude that the mdr2 P-glycoprotein has an essential role in the secretion of phosphatidylcholine into bile and hypothesize that it may be a phospholipid transport protein or phospholipid flippase.