Fournier N, Atger V, Paul J L, Moatti N
Laboratoire de biochimie, hôpital Broussais, Paris, France.
Ann Biol Clin (Paris). 1995;53(4):209-20.
Lipoprotein transport genes have been used to make either transgenic or knockout mice with altered lipoprotein levels and metabolism. These models have provided information in at least three major issues. First, transgenic mice allow to study gene expression regulation. This approach has been helpful in identifying tissue specific expression of two clusters of apolipoprotein genes apo E/CI/CII and apo AI/CIII/AIV. Another example is the identification of a cis-acting region controlling transcription of the CETP gene in response to diet. Second, transgenic mice model provides relevant insights into lipoprotein metabolism: the structural role of human apo AII, the effect of apo AI on HDL subfractions distribution, the contribution of apo CIII to hypertriglyceridemia, and by contrast of apo E in the clearance of atherogenic TG rich lipoproteins, the role of CETP in the balance of LDL and HDL concentration and distribution. Finally, certain strains of mice under specific conditions of diet develop atherosclerotic lesions which have been shown to be reduced in human apo AI transgenic animals. However, the best mouse model for further investigation of human atherosclerosis seems to be apo E knockout mice.
脂蛋白转运基因已被用于制造脂蛋白水平和代谢发生改变的转基因或基因敲除小鼠。这些模型在至少三个主要问题上提供了信息。首先,转基因小鼠有助于研究基因表达调控。这种方法有助于确定载脂蛋白基因apo E/CI/CII和apo AI/CIII/AIV两个簇的组织特异性表达。另一个例子是鉴定响应饮食控制的CETP基因转录的顺式作用区域。其次,转基因小鼠模型为脂蛋白代谢提供了相关见解:人类apo AII的结构作用、apo AI对HDL亚组分分布的影响、apo CIII对高甘油三酯血症的作用,以及与之形成对比的apo E在富含致动脉粥样硬化性甘油三酯脂蛋白清除中的作用、CETP在LDL和HDL浓度及分布平衡中的作用。最后,某些品系的小鼠在特定饮食条件下会形成动脉粥样硬化病变,而在人类apo AI转基因动物中这种病变已被证明会减少。然而,用于进一步研究人类动脉粥样硬化的最佳小鼠模型似乎是apo E基因敲除小鼠。