【作者】 韦玉生； 高俊； 黄粤； 刘德培； 刘光； 吴敏； 吴林； 张庆军； 张祝琴； 张然； 梁植权；

【Author】 Yusheng Wei, Jun Gao , Yue Huang, Depei Liu, Guang Liu, Min Wu , Lin Wu, Qingjun Zhang,Zhuqin Zhang, Ran Zhang, Chihchuan Liang (National Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences, Chinese Academy ofMedical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, P. R. China Address correspondence to: Depei Liu, Ph.D. National Laboratory of Medical Molecular Biology. Institute of Basic Medical Sciences. Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, P. R. China.

【机构】 中国医学科学院中国协和医科大学 医学分子生物学国家重点实验室；

【摘要】 <正>SUMMARYThe apolipoprotein (apo)AⅠ/CⅢ/AⅣgene cluster is involved in lipid metabolism and has a complex pattern of gene expression modulated by a common regulatory element, apoCⅢenhancer. A new member of this cluster, apoAⅤ, recently has been discovered as a novel modifier in triglyceride metabolism. To determine all the four apo genes expression in combination, most importantly, whether the transcription of apoAⅤis coregulated by apoCⅢenhancer in the cluster, we generated intact trans genie line carrying 116kb human apoAⅠ/CⅢ/AⅣ/AⅤgene cluster and mutant transgenic line in which apoCⅢenhancer was deleted from 116kb structure. We demonstrated that the apoCⅢenhancer regulated the hepatic and intestinal apoAⅠ, apoCⅢand apoAⅣexpression; however it did not direct the newly identified apoAⅤin the cluster. Furthermore, human apo genes displayed integrated position-independent and a closer approximation of copy number-dependent expression in the intact transgenic mice. As apoCⅢand apoAⅤplay opposite roles in triglyceride homeostasis, we analyzed the lipid profiles in our transgenic mice to assess the effects of human apoAⅠgene cluster expression on the lipid metabolism. Triglyceride level was elevated in intact transgenic mice, while decreased in mutant ones compared with nontransgenie mice. In addition, the expression of human apoAⅠand apoAⅣelevated HDL cholesterol in transgenic mice fed with atherogenic diet. In conclusion, our studies with human apoAⅠ/CⅢ/AⅣ/AⅤgene cluster transgenic models showed that apoCⅢenhancer regulated the expression of apoAⅠ, apoCⅢ, apoAⅣbut not apoAⅤin vivo and the influences of the entire cluster expression on the lipid metabolism.更多还原

【Abstract】 SUMMARYThe apolipoprotein (apo)AⅠ/CⅢ/AⅣ gene cluster is involved in lipid metabolism and has a complex pattern of gene expression modulated by a common regulatory element, apoCⅢ enhancer. A new member of this cluster, apoAⅤ, recently has been discovered as a novel modifier in triglyceride metabolism. To determine all the four apo genes expression in combination, most importantly, whether the transcription of apoAⅤ is coregulated by apoCⅢ enhancer in the cluster, we generated intact trans genie line carrying 116kb human apoAⅠ/CⅢ/AⅣ/AⅤ gene cluster and mutant transgenic line in which apoCⅢ enhancer was deleted from 116kb structure. We demonstrated that the apoCⅢ enhancer regulated the hepatic and intestinal apoAⅠ, apoCⅢ and apoAⅣ expression; however it did not direct the newly identified apoAⅤ in the cluster. Furthermore, human apo genes displayed integrated position-independent and a closer approximation of copy number-dependent expression in the intact transgenic mice. As apoCⅢ and apoAⅤ play opposite roles in triglyceride homeostasis, we analyzed the lipid profiles in our transgenic mice to assess the effects of human apoAⅠ gene cluster expression on the lipid metabolism. Triglyceride level was elevated in intact transgenic mice, while decreased in mutant ones compared with nontransgenie mice. In addition, the expression of human apoAⅠ and apoAⅣ elevated HDL cholesterol in transgenic mice fed with atherogenic diet. In conclusion, our studies with human apoAⅠ/CⅢ/AⅣ/AⅤ gene cluster transgenic models showed that apoCⅢ enhancer regulated the expression of apoAⅠ, apoCⅢ, apoAⅣ but not apoAⅤ in vivo and the influences of the entire cluster expression on the lipid metabolism.更多还原