{"title":"Using genetically engineered mice to understand apolipoprotein-B deficiency syndromes in humans.","authors":"M Raabe, E Kim, M Véniant, L B Nielsen, S G Young","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Several human diseases are characterized by defects in the synthesis and secretion of the apolipoprotein (apo) B-containing lipoproteins. Familial hypobetalipoproteinemia is caused by mutations in the apo-B gene and is characterized by abnormally low plasma concentrations of apo-B and low-density lipoprotein (LDL) cholesterol. Another apo-B deficiency syndrome, abetalipoproteinemia, is caused by mutations in the gene for microsomal triglyceride transfer protein (MTP). MTP is a microsomal protein that is thought to transfer lipids to the apo-B protein as it is translated, allowing it to attain the proper conformation for lipoprotein assembly. A third apo-B deficiency syndrome, Anderson's disease (or chylomicron retention disease), is characterized by the inability to secrete apo-B-containing chylomicrons from the intestine but an apparently normal capacity to secrete lipoproteins from the liver. To more fully understand these human apo-B deficiency syndromes, our laboratory has generated and characterized gene-targeted mouse models. This review summarizes what has been learned from these animal models.</p>","PeriodicalId":20612,"journal":{"name":"Proceedings of the Association of American Physicians","volume":"110 6","pages":"521-30"},"PeriodicalIF":0.0000,"publicationDate":"1998-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the Association of American Physicians","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Several human diseases are characterized by defects in the synthesis and secretion of the apolipoprotein (apo) B-containing lipoproteins. Familial hypobetalipoproteinemia is caused by mutations in the apo-B gene and is characterized by abnormally low plasma concentrations of apo-B and low-density lipoprotein (LDL) cholesterol. Another apo-B deficiency syndrome, abetalipoproteinemia, is caused by mutations in the gene for microsomal triglyceride transfer protein (MTP). MTP is a microsomal protein that is thought to transfer lipids to the apo-B protein as it is translated, allowing it to attain the proper conformation for lipoprotein assembly. A third apo-B deficiency syndrome, Anderson's disease (or chylomicron retention disease), is characterized by the inability to secrete apo-B-containing chylomicrons from the intestine but an apparently normal capacity to secrete lipoproteins from the liver. To more fully understand these human apo-B deficiency syndromes, our laboratory has generated and characterized gene-targeted mouse models. This review summarizes what has been learned from these animal models.
几种人类疾病的特点是载脂蛋白(apo) b -含脂蛋白的合成和分泌缺陷。家族性低脂蛋白血症是由载脂蛋白b基因突变引起的,其特征是血浆载脂蛋白b和低密度脂蛋白(LDL)胆固醇浓度异常低。另一种载脂蛋白b缺乏综合征,即脂蛋白血症,是由微粒体甘油三酯转移蛋白(MTP)基因突变引起的。MTP是一种微粒体蛋白,被认为在其翻译时将脂质转移到载脂蛋白b蛋白,使其获得适当的脂蛋白组装构象。第三种载脂蛋白b缺乏综合征,安德森病(或乳糜微粒滞留病),其特征是不能从肠道分泌含载脂蛋白b的乳糜微粒,但从肝脏分泌脂蛋白的能力明显正常。为了更充分地了解这些人类载脂蛋白b缺乏综合征,我们的实验室已经建立并表征了基因靶向小鼠模型。这篇综述总结了从这些动物模型中学到的东西。