Orsó E, Broccardo C, Kaminski W E, Böttcher A, Liebisch G, Drobnik W, Götz A, Chambenoit O, Diederich W, Langmann T, Spruss T, Luciani M F, Rothe G, Lackner K J, Chimini G, Schmitz G
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
Nat Genet. 2000 Feb;24(2):192-6. doi: 10.1038/72869.
Mutations in the gene encoding ATP-binding cassette transporter 1 ( ABC1) have been reported in Tangier disease (TD), an autosomal recessive disorder that is characterized by almost complete absence of plasma high-density lipoprotein (HDL), deposition of cholesteryl esters in the reticulo-endothelial system (RES) and aberrant cellular lipid trafficking. We demonstrate here that mice with a targeted inactivation of Abc1 display morphologic abnormalities and perturbations in their lipoprotein metabolism concordant with TD. ABC1 is expressed on the plasma membrane and the Golgi complex, mediates apo-AI associated export of cholesterol and phospholipids from the cell, and is regulated by cholesterol flux. Structural and functional abnormalities in caveolar processing and the trans-Golgi secretory pathway of cells lacking functional ABC1 indicate that lipid export processes involving vesicular budding between the Golgi and the plasma membrane are severely disturbed.
据报道，编码ATP结合盒转运蛋白1（ABC1）的基因突变与丹吉尔病（TD）有关，TD是一种常染色体隐性疾病，其特征为血浆高密度脂蛋白（HDL）几乎完全缺失、网状内皮系统（RES）中胆固醇酯沉积以及细胞脂质转运异常。我们在此证明，Abc1基因被靶向失活的小鼠表现出与TD一致的形态学异常和脂蛋白代谢紊乱。ABC1在质膜和高尔基体复合物上表达，介导载脂蛋白AI相关的胆固醇和磷脂从细胞内输出，并受胆固醇通量调节。缺乏功能性ABC1的细胞在小窝加工和反式高尔基体分泌途径中存在结构和功能异常，这表明涉及高尔基体和质膜之间囊泡出芽的脂质输出过程受到严重干扰。
