文章基本信息

标题：Targeted disruption of the murine mucin gene 1 decreases susceptibility to cholesterol gallstone formation
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作者：Helen H. Wang ; Nezam H. Afdhal ; Sandra J. Gendler 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2004
卷号：45
期号：3
页码：438-447
DOI：10.1194/jlr.M300468-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Gallbladder mucins play a critical role in the pathogenesis of cholesterol gallstones because of their ability to bind biliary lipids and accelerate cholesterol crystallization. Mucin secretion and accumulation in the gallbladder is determined by multiple mucin genes. To study whether mucin gene 1 ( Muc1 ) influences susceptibility to cholesterol cholelithiasis, we investigated male Muc1 -deficient ( Muc1 ⁻ ^/ ⁻) and wild-type mice fed a lithogenic diet containing 1% cholesterol and 0.5% cholic acid for 56 days. Gene expression of the gallbladder Muc1 and Muc5ac was significantly reduced in Muc1 ⁻ ^/ ⁻ mice in response to the lithogenic diet. Muc3 and Muc4 levels were upregulated and were similar between Muc1 ⁻ ^/ ⁻ and wild-type mice. Little or no Muc2 and Muc5b mRNAs were detected. Muc1 ⁻ ^/ ⁻ mice displayed significant decreases in total mucin secretion and accumulation in the gallbladder as well as retardation of crystallization, growth, and agglomeration of cholesterol monohydrate crystals. At 56 days of feeding, gallstone prevalence was decreased by 40% in Muc1 ⁻ ^/ ⁻ mice. However, cholesterol saturation indices of gallbladder biles, hepatic secretion of biliary lipids, and gallbladder size were comparable in Muc1 ⁻ ^/ ⁻ and wild-type mice. We conclude that decreased gallstone formation in mice with disrupted Muc1 gene results from reduced mucin secretion and accumulation in the gallbladder.