Raabe M, Kim E, Véniant M, Nielsen L B, Young S G
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100, USA.
Proc Assoc Am Physicians. 1998 Nov-Dec;110(6):521-30.
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.
几种人类疾病的特征是含载脂蛋白（apo）B的脂蛋白合成和分泌存在缺陷。家族性低β脂蛋白血症由apo - B基因突变引起，其特征是血浆中apo - B和低密度脂蛋白（LDL）胆固醇浓度异常低。另一种apo - B缺乏综合征，即无β脂蛋白血症，是由微粒体甘油三酯转移蛋白（MTP）基因的突变引起的。MTP是一种微粒体蛋白，被认为在apo - B蛋白翻译时将脂质转移给它，使其获得脂蛋白组装所需的正确构象。第三种apo - B缺乏综合征，安德森病（或乳糜微粒滞留病），其特征是无法从肠道分泌含apo - B的乳糜微粒，但肝脏分泌脂蛋白的能力显然正常。为了更全面地了解这些人类apo - B缺乏综合征，我们实验室构建并鉴定了基因靶向小鼠模型。本综述总结了从这些动物模型中学到的知识。
