Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis
Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis
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DOI：
10.1002/hep.510230435
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发表时间：
1996-04-01
期刊：
影响因子：
13.5
通讯作者：
Hadchouel, M
中科院分区：
文献类型：
--
作者：
Deleuze, JF;Jacquemin, E;Hadchouel, M
鼠mdr 2的破坏在遗传性人类胆汁淤积症中，具有高γ-谷氨酰转肽酶（GGT）血清活性的进行性家族性肝内胆汁淤积症的亚型具有相同的组织学、生物化学、免疫组织化学和细胞生物学特征，以及缺乏mdr 2基因表达的小鼠（mdr 2-/-小鼠）的遗传特征。通过北方印迹法在患有这种形式的PFIC的患者的肝脏中未检测到MDR 3（人mdr 2同系物）信使RNA（mRNA），并且第二名患者的胆汁磷脂水平显著降低。因此，MDR 3 β-糖蛋白的缺乏可能是导致这种PFIC的原因，与鼠模型中一样，这可能是由于在缺乏胆汁磷脂的情况下胆汁酸对胆管上皮的毒性作用。
Disruption of the murine mdr2 (multidrug-resistance) gene, which encodes a phosphatidylcholine flippase, leads to a hepatic disorder because of loss of biliary phospholipid secretion, Among the hereditary human cholestasis, a subtype of progressive familial intrahepatic cholestasis with high gamma-glutamyltranspeptidase (GGT) serum activity shares histological, biochemical, and genetic features with mice lacking mdr2 gene expression (mdr2 -/- mice). No MDR3 (human mdr2 homolog) messenger RNA (mRNA) was detected by Northern blotting in the liver of a patient suffering from this form of PFIC, and the biliary phospholipid level in a second patient was substantially decreased. Thus, the absence of the MDR3 beta-glycoprotein may be responsible for this type of PFIC, which, as in the murine model, may be due to a toxic effect of bile acids on the biliary epithelium in absence of biliary phospholipids.