Swanson M E, Hughes T E, Denny I S, France D S, Paterniti J R, Tapparelli C, Gfeller P, Bürki K
Department of Molecular Biology, Sandoz Research Institute, East Hanover, NJ 07936.
Transgenic Res. 1992 May;1(3):142-7. doi: 10.1007/BF02528779.
To examine the consequences of increased apolipoprotein A-I production on cholesterol and lipoprotein metabolism, we have produced two lines of transgenic rats; one expressing moderate and one very high levels of human apolipoprotein A-I. The rats were produced by microinjection of a 13 kbp DNA fragment containing the human apolipoprotein A-I gene plus 10 kbp of its 5' flanking sequence and 1 kbp of its 3' flanking sequence. Both lines of transgenic rats express human apolipoprotein A-I mRNA in liver and human apolipoprotein A-I in plasma. Sera from these rats contain significantly higher levels of total apolipoprotein A-I, high density lipoprotein cholesterol and phospholipid than sera from non-transgenic littermates. Transgenic rats expressing high levels of human apolipoprotein A-I have reduced levels of serum rat apolipoprotein A-I suggesting a mechanism exists to down-regulate apolipoprotein A-I production. These transgenic rats provide a unique animal model to examine the effects of increased apolipoprotein A-I production on lipid and lipoprotein metabolism.
为了研究载脂蛋白A-I生成增加对胆固醇和脂蛋白代谢的影响，我们培育了两系转基因大鼠；一系表达中等水平的人载脂蛋白A-I，另一系表达非常高水平的人载脂蛋白A-I。这些大鼠是通过显微注射一个13kbp的DNA片段培育而成的，该片段包含人载脂蛋白A-I基因及其5'侧翼序列的10kbp和3'侧翼序列的1kbp。两系转基因大鼠在肝脏中均表达人载脂蛋白A-I mRNA，在血浆中均表达人载脂蛋白A-I。这些大鼠的血清中总载脂蛋白A-I、高密度脂蛋白胆固醇和磷脂水平显著高于非转基因同窝仔鼠的血清。表达高水平人载脂蛋白A-I的转基因大鼠血清中大鼠载脂蛋白A-I水平降低，提示存在一种下调载脂蛋白A-I生成的机制。这些转基因大鼠为研究载脂蛋白A-I生成增加对脂质和脂蛋白代谢的影响提供了独特的动物模型。
