【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.