Transgenic rabbits expressing human lipoprotein lipase
Transgenic rabbits expressing human lipoprotein lipase
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DOI：
10.1023/a:1008115429679
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发表时间：
2000-07-01
期刊：
影响因子：
2.2
通讯作者：
Watanabe, T
中科院分区：
文献类型：
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作者：
Araki, M;Fan, JL;Watanabe, T
为了研究脂蛋白脂酶（LPL）在脂质和脂蛋白代谢中的作用及其与动脉粥样硬化的关系，我们制备了表达人LPL基因的转基因兔。将含有鸡β-肌动蛋白启动子、人LPL cDNA和带有poly（A）信号的兔β-珠蛋白的3.8-kb SalI/HindIII片段显微注射到总共4045只日本白色兔胚胎中，然后移植到116只受体兔中。在出生的166只幼仔中，6只幼仔经Southern印迹分析证实为转基因。北方印迹分析显示，人LPL在许多组织中表达，包括心脏、肾脏、肾上腺和肠。一只转基因兔显示肝素后血浆中LPL活性比非转基因兔高3倍。通过原位杂交和免疫组化进一步证实了转基因兔不同组织中人LPL的表达。由于兔作为动脉粥样硬化模型上级小鼠，该转基因兔模型为LPL在脂质代谢和动脉粥样硬化中的研究提供了有价值的工具。
To study the functions of lipoprotein lipase (LPL) in lipid and lipoprotein metabolism and the relationship between LPL and atherosclerosis, we generated transgenic rabbits expressing the human LPL gene. A total of 4045 Japanese white rabbit embryos were microinjected with a 3.8-kb SalI/HindIII fragment containing the chicken beta-actin promoter, human LPL cDNA and rabbit beta-globin with poly (A) signals, and then transplanted into 116 recipient rabbits. Of the 166 pups born, six pups were transgenic as confirmed by Southern blot analysis. A Northern blot analysis revealed that human LPL was expressed by a number of tissues including the heart, kidney, adrenal gland and intestine. One transgenic rabbit showed up to 3-fold increased LPL activity in post-heparin plasma compared to that in nontransgenic rabbits. Human LPL expression in various tissues of transgenic rabbits was further elucidated by in situ hybridization and immunostaining. Since rabbits are superior to mice as a model of atherosclerosis, this transgenic rabbit model should provide a valuable tool for the study of LPL in lipid metabolism and atherosclerosis.