Frazer K A, Narla G, Zhang J L, Rubin E M
Human Genome Center, Lawrence Berkeley Laboratory, University of California, Berkeley 94720, USA.
Nat Genet. 1995 Apr;9(4):424-31. doi: 10.1038/ng0495-424.
High plasma concentrations of apolipoprotein (a) (apo(a)) have been implicated as a major independent risk factor for atherosclerosis in humans. Apo(a) is a large, evolutionarily new gene (present primarily in primates) for which considerable controversy exists concerning the factors that regulate its expression. To investigate the in vivo regulation of apo(a), we have created several lines of YAC transgenic mice containing a 110-kb human apo(a) gene surrounded by greater than 60 kb of 5' and 3' flanking DNA. Studies in humans have suggested that acute-phase inducers increase and sex steroids decrease apo(a) concentrations, but these results are controversial. Analysis of the YAC transgenic mice conclusively supports the hypothesized role of sex steroids and refutes the suggested role of acute-phase inducers in regulating the apo(a) gene.
血浆中载脂蛋白(a)[apo(a)]的高浓度被认为是人类动脉粥样硬化的主要独立危险因素。apo(a)是一个大型的、进化上新出现的基因（主要存在于灵长类动物中），关于调节其表达的因素存在相当大的争议。为了研究apo(a)在体内的调节机制，我们构建了几个YAC转基因小鼠品系，这些小鼠含有一个110kb的人类apo(a)基因，其两侧有超过60kb的5'和3'侧翼DNA。对人类的研究表明，急性期诱导剂会增加而性类固醇会降低apo(a)的浓度，但这些结果存在争议。对YAC转基因小鼠的分析最终支持了性类固醇的假设作用，并驳斥了急性期诱导剂在调节apo(a)基因中的作用。
