Transgenic overexpression of Abcb11 enhances biliary bile salt outputs, but does not affect cholesterol cholelithogenesis in mice.
Transgenic overexpression of Abcb11 enhances biliary bile salt outputs, but does not affect cholesterol cholelithogenesis in mice.
复制标题
Abcb11 的转基因过表达可增强小鼠胆汁胆汁盐的输出，但不影响胆固醇胆石生成。
DOI：
10.1111/j.1365-2362.2010.02300.x
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发表时间：
2010
影响因子：
5.5
通讯作者：
Wang,DavidQ-H
中科院分区：
文献类型：
--
作者：
Wang,HelenH;Lammert,Frank;Schmitz,Anne;Wang,DavidQ-H
欧洲临床投资杂志 2010； 40 (6): 541–551摘要背景胆固醇胆石病是一种复杂的遗传性状，由多种但迄今未知的基因诱发。与耐药 AKR 小鼠相比，在胆结石易感性 C57L 小鼠的 2 号染色体上首次发现了主要的 Lith 基因 Lith1。Abcb11 编码肝细胞中的小管胆汁盐输出泵，与 Lith1 QTL 区域共定位，其在 C57L 小鼠中的肝脏表达显着高于 AKR 小鼠。材料和方法为了研究 Abcb11 是否影响胆固醇胆结石的形成，我们创建了在AKR遗传背景上建立Abcb11转基因品系，并用生石饮食喂养这些小鼠56天。结果我们排除了C57L和AKR小鼠之间Abcb11基因及其启动子区域的功能相关多态性。 Abcb11 的过度表达显着促进胆汁胆盐分泌，增加循环胆汁盐库大小和胆盐依赖性胆汁流速。然而，转基因小鼠和野生型小鼠的胆汁胆固醇和磷脂分泌以及胆囊大小和收缩力相当。生石饮食第56天时，两组小鼠胆囊胆汁胆固醇饱和度指数和胆结石患病率基本相似。结论Abcb11过表达增加胆汁胆盐分泌，但不影响小鼠胆石形成。
Eur J Clin Invest 2010; 40 (6): 541–551AbstractBackgroundCholesterol gallstone disease is a complex genetic trait and induced by multiple but as yet unknown genes. A majorLithgene,Lith1was first identified on chromosome 2 in gallstone‐susceptible C57L mice compared with resistant AKR mice.Abcb11, encoding the canalicular bile salt export pump in the hepatocyte, co‐localizes with theLith1QTL region and its hepatic expression is significantly higher in C57L mice than in AKR mice.Material and methodsTo investigate whetherAbcb11influences cholesterol gallstone formation, we created anAbcb11transgenic strain on the AKR genetic background and fed these mice with a lithogenic diet for 56 days.ResultWe excluded functionally relevant polymorphisms of theAbcb11gene and its promoter region between C57L and AKR mice. Overexpression ofAbcb11significantly promoted biliary bile salt secretion and increased circulating bile salt pool size and bile salt‐dependent bile flow rate. However, biliary cholesterol and phospholipid secretion, as well as gallbladder size and contractility were comparable in transgenic and wild‐type mice. At 56 days on the lithogenic diet, cholesterol saturation indexes of gallbladder biles and gallstone prevalence rates were essentially similar in these two groups of mice.ConclusionOverexpression ofAbcb11augments biliary bile salt secretion, but does not affect cholelithogenesis in mice.